Cognitive Inflexibility after Prefrontal Serotonin Depletion Is Behaviorally and Neurochemically Specific
Abstract
We have previously demonstrated that prefrontal serotonin depletion impairs orbitofrontal cortex (OFC)-mediated serial discrimination reversal (SDR) learning but not lateral prefrontal cortex (PFC)-mediated attentional set shifting. To address the neurochemical specificity of this reversal deficit, Experiment 1 compared the effects of selective serotonin and selective dopamine depletions of the OFC on performance of the SDR task. Whereas serotonin depletions markedly impaired performance, OFC dopamine depletions were without effect. The behavioral specificity of this reversal impairment was investigated in Experiment 2 by examining the effect of OFC serotonin depletion on performance of a modified SDR task designed to distinguish between 3 possible causes of the impairment. The results showed that the reversal deficit induced by prefrontal serotonin depletion was not due to a failure to approach a previously unrewarded stimulus (enhanced learned avoidance) or reduced proactive interference. Instead, it was due specifically to a failure to inhibit responding to the previously rewarded stimulus. The neurochemical and behavioral specificity of this particular form of cognitive inflexibility is of particular relevance to our understanding of the aetiology and treatment of inflexible behavior apparent in many neuropsychiatric and neurodegenerative disorders involving the PFC.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In marmoset monkeys, targeted neurotoxic serotonin depletion of the orbito-frontal cortex, but not of the caudate nucleus, consistently produced reversal deficits.
“In marmoset monkeys, targeted neurotoxic serotonin depletion of the orbito-frontal cortex, but not of the caudate nucleus, consistently produced reversal deficits [5, 6].”
From Chronic escitalopram in healthy volunteers has specific effects on reinforcement sensitivity: a double-blind, placebo-controlled semi-randomised study (2023) · cites this paper as [6]
The Discussion reports reversal-learning deficits after serotonin depletion in marmoset OFC and lateral PFC, and the Serial reversal section reports more errors across reversals. The paper does not report a comparison with targeted serotonin depletion of the caudate nucleus; its comparison is with dopamine depletion of the OFC. It also notes that serotonin depletion was not restricted to the OFC. (LLM, conf=0.89)
Experimental — accuracy not yet measuredSerotonin is released in the PFC during exposure to uncontrollable stress and is key to orbital PFC function.
“For example, important work is underway to reveal the complex and powerful effects on prefrontal functions of serotonin, another modulator that is released in the PFC during exposure to uncontrollable stress158 and that is key to orbital PFC function159.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [159]
Work in animals has shown decreased sensitivity to outcome devaluation as a result of serotonin receptor antagonism or serotonin depletion.
“but work in animals has shown decreased sensitivity to outcome devaluation as a result of serotonin receptor antagonism or serotonin depletion 34, 35.”
From Enhanced avoidance habits in obsessive-compulsive disorder (2014) · cites this paper as [34]
Depletion of dopamine in the striatum, but not the OFC, caused reversal learning deficits in marmosets.
“Depletion of dopamine in this brain region, but not in the OFC, caused deficits in marmosets (Clarke et al 2011, Clarke et al 2007)”
From Prefrontal cortex executive processes affected by stress in health and disease (2018) · cites this paper as Clarke et al 2007
The authors' results and framework, including how learning from worse-than-expected outcomes is affected, agree with earlier observations and manipulations of serotonin neurons.
“Our findings and conceptual framework, including the effect on learning from worse-than-expected outcomes, are consistent with previous observations and manipulations of serotonin neuron activity.”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [38]
When action-outcome contingencies were reversed, lesions or drugs targeting serotonin neurons impaired adaptive behavior at reversal.
“In reversal tasks in which action-outcome contingencies were switched, lesions or pharmacological manipulations of serotonin neurons also resulted in impairments of adaptive behavior at the time of reversal.37–41”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [38]
Serotonin axon lesions or reversible inactivation of dorsal raphe serotonin neurons impaired behavioral adaptation to changes in action- or stimulus-outcome mappings.
“Serotonin axon lesions37,38 or reversible inactivation of dorsal raphe serotonin neurons33 impaired behavioral adaptation to changes in action- or stimulus-outcome mappings.”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [38]
Prior research demonstrates that serotonin neurons modulate flexible behavior in changing environments.
“Prior research demonstrates that serotonin neurons modulate flexible behavior in changing environments.33,37–42”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [38]
Animals with lesions kept performing the action that had been rewarded before.
“Specifically, lesioned animals continued to make the previously rewarded action.”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Parallel organization of functionally segregated circuits linking basal ganglia and cortex
Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.09.030186.002041 · Cited by 8,527 · see citing works
Getting formal with dopamine and reward
Schultz, W. (2002) · Neuron · doi:10.1016/s0896-6273(02)00967-4 · Cited by 2,574 · see citing works
The Psychology of Animal Learning
Hill, W. F., & Mackintosh, N. J. (1976) · The American Journal of Psychology · doi:10.2307/1421765 · Cited by 2,397 · see citing works
Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex
Cardinal, R. N., Parkinson, J. A., Hall, J., & Everitt, B. J. (2002) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(02)00007-6 · Cited by 2,129 · see citing works
The psychology of animal learning
Lea, S. E. G. (1975) · Animal Behaviour · doi:10.1016/0003-3472(75)90150-5 · Cited by 2,067 · see citing works
Abstract reward and punishment representations in the human orbitofrontal cortex
O'Doherty, J., Kringelbach, M. L., Rolls, E. T., Hornak, J., & Andrews, C. (2001) · Nature Neuroscience · doi:10.1038/82959 · Cited by 2,003 · see citing works
Uneven Pattern of Dopamine Loss in the Striatum of Patients with Idiopathic Parkinson's Disease
Kish, S. J., Shannak, K. S., & Hornykiewicz, O. (1988) · New England Journal of Medicine · doi:10.1056/nejm198804073181402 · Cited by 1,945 · see citing works
Dissociation in prefrontal cortex of affective and attentional shifts
Dias, R., Robbins, T. W., & Roberts, A. C. (1996) · Nature · doi:10.1038/380069a0 · Cited by 1,527 · see citing works
Self-citationChanges in brain activity related to eating chocolate: From pleasure to aversion
Small, D. M. (2001) · Brain · doi:10.1093/brain/124.9.1720 · Cited by 1,179 · see citing works
Rolls, E. T., Hornak, J., Wade, D., & McGrath, J. (1994) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.57.12.1518 · Cited by 1,005 · see citing works
Cools, R. (2001) · Cerebral Cortex · doi:10.1093/cercor/11.12.1136 · Cited by 906 · see citing works
Cools, R. (2006) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.03.024 · Cited by 903 · see citing works
Elliott, R. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.3.308 · Cited by 887 · see citing works
Limbic lesions and the problem of stimulus--reinforcement associations.
Jones, B., & Mishkin, M. (1972) · Experimental Neurology · doi:10.1016/0014-4886(72)90030-1 · Cited by 864 · see citing works
‘Frontal' cognitive function in patients with Parkinson's disease ‘on' and ‘off' levodopa
GOTHAM, A. M., BROWN, R. G., & MARSDEN, C. D. (1988) · Brain · doi:10.1093/brain/111.2.299 · Cited by 835 · see citing works
Neuroimaging and frontal–subcortical circuitry in obsessive–compulsive disorder
Saxena, S., Brody, A. L., Schwartz, J. M., & Baxter, L. R. (1998) · British Journal of Psychiatry · doi:10.1192/s0007125000297870 · Cited by 831 · see citing works
Handbook of Contemporary Learning Theories
Mowrer, R. R. (2000) · Psychology Press eBooks · doi:10.4324/9781410600691 · Cited by 789 · see citing works
Serotonin receptors : their key role in drugs to treat schizophrenia
Meltzer, H. Y., Li, Z., Kaneda, Y., & Ichikawa, J. (2003) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2003.09.010 · Cited by 778 · see citing works
Iversen, S., & Mishkin, M. (1970) · Experimental Brain Research · doi:10.1007/bf00237911 · Cited by 765 · see citing works
Cognitive Inflexibility After Prefrontal Serotonin Depletion
Clarke, H. F., Dalley, J. W., Crofts, H. S., Robbins, T. W., & Roberts, A. C. (2004) · Science · doi:10.1126/science.1094987 · Cited by 632 · see citing works
Self-citationLange, K. W., Robbins, T. W., MARSDEN, C. D., James-Galton, M., Owen, A. M., & Paul, G. M. (1992) · Psychopharmacology · doi:10.1007/bf02245167 · Cited by 608 · see citing works
Self-citationHornak, J., O'Doherty, J., Bramham, J., Rolls, E. T., Morris, R. G., Bullock, P. R., & Polkey, C. E. (2004) · Journal of Cognitive Neuroscience · doi:10.1162/089892904322926791 · Cited by 603 · see citing works
Swainson, R., Rogers, R. D., Sahakian, B. J., Summers, B. A., Polkey, C. E., & Robbins, T. W. (2000) · Neuropsychologia · doi:10.1016/s0028-3932(99)00103-7 · Cited by 486 · see citing works
Self-citationDias, R. S., Robbins, T. W., & Roberts, A. (1996) · Behavioral Neuroscience · doi:10.1037//0735-7044.110.5.872 · Cited by 477 · see citing works
Self-citationDias, R., Robbins, T. W., & Roberts, A. C. (1996) · Behavioral Neuroscience · doi:10.1037/0735-7044.110.5.872 · Cited by 476 · see citing works
Self-citationRogers, R. D., Andrews, T. C., Grasby, P. M., Brooks, D. J., & Robbins, T. W. (2000) · Journal of Cognitive Neuroscience · doi:10.1162/089892900561931 · Cited by 458 · see citing works
Self-citationRoberts, A., De Salvia, M., Wilkinson, L., Collins, P., Muir, J., Everitt, B., & Robbins, T. (1994) · The Journal of Neuroscience · doi:10.1523/jneurosci.14-05-02531.1994 · Cited by 415 · see citing works
Self-citationButter, C. M. (1969) · Physiology & Behavior · doi:10.1016/0031-9384(69)90075-4 · Cited by 395 · see citing works
Saxena, S. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00082-2 · Cited by 379 · see citing works
Winstanley, C. A., Dalley, J. W., Theobald, D. E., & Robbins, T. W. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300434 · Cited by 371 · see citing works
Self-citationPrefrontal Serotonin Depletion Affects Reversal Learning But Not Attentional Set Shifting
Clarke, H. F., Walker, S. C., Crofts, H. S., Dalley, J. W., Robbins, T. W., & Roberts, A. C. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3690-04.2005 · Cited by 358 · see citing works
Self-citationComparison of set-shifting ability in patients with chronic schizophrenia and frontal lobe damage
Pantelis, C., Barber, F. Z., Barnes, T. R. E., Nelson, H. E., Owen, A. M., & Robbins, T. W. (1999) · Schizophrenia Research · doi:10.1016/s0920-9964(98)00156-x · Cited by 347 · see citing works
Self-citationTryptophan depletion in normal volunteers produces selective impairments in learning and memory
Park, S. B., Coull, J. T., McShane, R. H., Young, A. H., Sahakian, B. J., Robbins, T. W., & Cowen, P. J. (1994) · Neuropharmacology · doi:10.1016/0028-3908(94)90089-2 · Cited by 310 · see citing works
Self-citationRoberts, A., Robbins, T. W., & Everitt, B. J. (1988) · PubMed · Cited by 306 · see citing works
Self-citationRogers, R. D., Blackshaw, A. J., Middleton, H. C., Matthews, K., Hawtin, K., Crowley, C., Hopwood, A., Wallace, C., Deakin, J. F. W., Sahakian, B. J., et al. (1999) · Psychopharmacology · doi:10.1007/pl00005494 · Cited by 289 · see citing works
Self-citationCrofts, H. S. (2001) · Cerebral Cortex · doi:10.1093/cercor/11.11.1015 · Cited by 284 · see citing works
Winstanley, C. A., Theobald, D. E. H., Dalley, J. W., Cardinal, R. N., & Robbins, T. W. (2005) · Cerebral Cortex · doi:10.1093/cercor/bhi088 · Cited by 279 · see citing works
Self-citationJentsch, D. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00355-4 · Cited by 272 · see citing works
Limbic Corticostriatal Systems and Delayed Reinforcement
Cardinal, R. N., Winstanley, C. A., Robbins, T. W., & Everitt, B. J. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1308.004 · Cited by 266 · see citing works
Self-citationANOVA for the Behavioral Sciences Researcher
Cardinal, R. N., & Aitken, M. R. F. (2013) · Psychology Press eBooks · doi:10.4324/9780203763933 · Cited by 249 · see citing works
Mehta, M. A., Swainson, R., Ogilvie, A. D., Sahakian, B., & Robbins, T. W. (2001) · Psychopharmacology · doi:10.1007/s002130100851 · Cited by 235 · see citing works
Self-citationEvers, E. A. T., Cools, R., Clark, L., van der Veen, F. M., Jolles, J., Sahakian, B. J., & Robbins, T. W. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300663 · Cited by 208 · see citing works
Self-citationClark, L., Roiser, J. P., Cools, R., Rubinsztein, D. C., Sahakian, B. J., & Robbins, T. W. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0104-6 · Cited by 175 · see citing works
Self-citationOrbitofrontal function, object alternation and perseveration
Freedman, M. (1998) · Cerebral Cortex · doi:10.1093/cercor/8.1.18 · Cited by 165 · see citing works
Abbruzzese, M., Bellodi, L., Ferri, S., & Scarone, S. (1995) · Brain and Cognition · doi:10.1006/brcg.1995.1017 · Cited by 164 · see citing works
Crean, J. P., Richards, J. B., & de Wit, H. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00132-8 · Cited by 155 · see citing works
LeMarquand, D. G., Benkelfat, C., Pihl, R. O., Palmour, R. M., & Young, S. N. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.11.1771 · Cited by 150 · see citing works
Are dopaminergic neurons selectively vulnerable to Parkinson's disease?
Agid, Y., Ruberg, M., Javoy-Agid, F., Hirsch, É. C., Raisman‐Vozari, R., Vyas, S., Faucheux, B. A., Michel, P. P., Kästner, A., & Blanchard, V. (1993) · PubMed · Cited by 127 · see citing works
Kheramin, S., Body, S., Ho, M.-Y., Vel�zquez-Martinez, D. N., Bradshaw, C. M., Szabadi, E., Deakin, J. F. W., & Anderson, I. M. (2004) · Psychopharmacology · doi:10.1007/s00213-004-1813-y · Cited by 117 · see citing works
Tryptophan Depletion, Executive Functions, and Disinhibition in Aggressive, Adolescent Males
LeMarquand, D. G., Pihl, R. O., Young, S. N., Tremblay, R. E., Séguin, J. R., Palmour, R. M., & Benkelfat, C. (1998) · Neuropsychopharmacology · doi:10.1016/s0893-133x(98)00029-3 · Cited by 110 · see citing works
Tryptophan Depletion, Executive Functions, and Disinhibition in Aggressive, Adolescent Males
LeMarquand, D. G., Pihl, R. O., Young, S. N., Tremblay, R. E., Séguin, J. R., Palmour, R. M., & Benkelfat, C. (1998) · Neuropsychopharmacology · doi:10.1038/sj.npp.1395196 · Cited by 88 · see citing works
Cetin, T., Freudenberg, F., Füchtemeier, M., & Koch, M. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.08.002 · Cited by 68 · see citing works
Oades, R. D., Slusarek, M., Veiling, S., & Bondy, B. (2002) · The World Journal of Biological Psychiatry · doi:10.3109/15622970209150607 · Cited by 44 · see citing works
Rescorla, R. A. (2000) · PsycEXTRA Dataset · doi:10.1037/e413792005-865 · Cited by 33 · see citing works
Perseveration and over-switching in schizophrenia
Yogev, H., Hadar, U., Gutman, Y., & Sirota, P. (2003) · Schizophrenia Research · doi:10.1016/s0920-9964(02)00323-7 · Cited by 32 · see citing works
Assessment of the role of transfer suppression in learning-set formation in monkeys.
Conner, J. B., & Meyer, D. R. (1971) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0030690 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Stress signalling pathways that impair prefrontal cortex structure and function
Arnsten, A. F. T. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2648 · Cited by 3,299 · see citing works
Inhibition and impulsivity: behavioral and neural basis of response control
Bari, A., & Robbins, T. W. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.06.005 · Cited by 1,921 · see citing works
Self-citationThe Neuropsychopharmacology of Fronto-Executive Function: Monoaminergic Modulation
Robbins, T. W., & Arnsten, A. F. T. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135535 · Cited by 957 · see citing works
Self-citationSerotonin and brain function: a tale of two receptors
Carhart-Harris, R., & Nutt, D. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117725915 · Cited by 739 · see citing works
The neural basis of reversal learning: An updated perspective
Izquierdo, A., Brigman, J. L., Radke, A. K., Rudebeck, P. H., & Holmes, A. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2016.03.021 · Cited by 670 · see citing works
Serotoninergic regulation of emotional and behavioural control processes
Cools, R., Roberts, A. C., & Robbins, T. W. (2008) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2007.10.011 · Cited by 656 · see citing works
Self-citationProbing compulsive and impulsive behaviors, from animal models to endophenotypes: A narrative review
Fineberg, N. A., Potenza, M. N., Chamberlain, S. R., Berlin, H. A., Menzies, L., Bechara, A., Sahakian, B. J., Robbins, T. W., Bullmore, E. T., & Hollander, E. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.185 · Cited by 654 · see citing works
Self-citationDoya, K. (2008) · Nature Neuroscience · doi:10.1038/nn2077 · Cited by 642 · see citing works
Neurophysiology of performance monitoring and adaptive behavior
Ullsperger, M., Danielmeier, C., & Jocham, G. (2014) · Physiological Reviews · doi:10.1152/physrev.00041.2012 · Cited by 634 · see citing works
Gillan, C. M., Papmeyer, M., Morein-Zamir, S., Sahakian, B. J., Fineberg, N. A., Robbins, T. W., & de Wit, S. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10071062 · Cited by 609 · see citing works
Self-citationMouse Behavioral Assays Relevant to the Symptoms of Autism*
Crawley, J. N. (2007) · Brain Pathology · doi:10.1111/j.1750-3639.2007.00096.x · Cited by 541 · see citing works
Obsessive-compulsive disorder: Puzzles and prospects
Robbins, T. W., Vaghi, M. M., & Banca, P. (2019) · Neuron · doi:10.1016/j.neuron.2019.01.046 · Cited by 510 · see citing works
Self-citationLogue, S. F., & Gould, T. J. (2014) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.08.007 · Cited by 477 · see citing works
Serotonin and dopamine: unifying affective, activational, and decision functions.
Cools, R., Nakamura, K., & Daw, N. D. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.121 · Cited by 464 · see citing works
Opponency revisited: competition and cooperation between dopamine and serotonin
Boureau, Y.-L., & Dayan, P. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.151 · Cited by 456 · see citing works
Robbins, T. W. (2007) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2007.2097 · Cited by 413 · see citing works
Self-citationEnhanced avoidance habits in obsessive-compulsive disorder
Gillan, C. M., Morein-Zamir, S., Urcelay, G. P., Sule, A., Voon, V., Apergis-Schoute, A. M., Fineberg, N. A., Sahakian, B. J., & Robbins, T. W. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.02.002 · Cited by 399 · see citing works
Self-citationBondi, C. O., Rodriguez, G., Gould, G. G., Frazer, A., & Morilak, D. A. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301410 · Cited by 398 · see citing works
Learning and cognitive flexibility: frontostriatal function and monoaminergic modulation
Kehagia, A. A., Murray, G. K., & Robbins, T. W. (2010) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2010.01.007 · Cited by 398 · see citing works
Self-citationSerotonin in Affective Control
Dayan, P., & Huys, Q. J. M. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135607 · Cited by 381 · see citing works
Bissonette, G. B., Martins, G. J., Franz, T. M., Harper, E. S., Schoenbaum, G., & Powell, E. M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2820-08.2008 · Cited by 353 · see citing works
Neuroinflammation as a risk factor for attention deficit hyperactivity disorder
Dunn, G. A., Nigg, J. T., & Sullivan, E. L. (2019) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2019.05.005 · Cited by 299 · see citing works
Dissecting impulsivity and its relationships to drug addictions
Jentsch, J. D., Ashenhurst, J. R., Cervantes, M. C., Groman, S. M., James, A. S., & Pennington, Z. T. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12388 · Cited by 281 · see citing works
Clarke, H. F., Robbins, T. W., & Roberts, A. C. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1521-08.2008 · Cited by 263 · see citing works
Self-citationActivity patterns of serotonin neurons underlying cognitive flexibility
Matias, S., Lottem, E., Dugué, G. P., & Mainen, Z. F. (2017) · eLife · doi:10.7554/elife.20552 · Cited by 239 · see citing works
Boulougouris, V., Glennon, J. C., & Robbins, T. W. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301584 · Cited by 219 · see citing works
Self-citationDopaminergic control of cognitive flexibility in humans and animals
Klanker, M., Feenstra, M., & Denys, D. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00201 · Cited by 209 · see citing works
Brigman, J. L., Mathur, P., Harvey-White, J., Izquierdo, A., Saksida, L. M., Bussey, T. J., Fox, S., Deneris, E., Murphy, D. L., & Holmes, A. (2010) · Cerebral Cortex · doi:10.1093/cercor/bhp266 · Cited by 184 · see citing works
Lesions of the dorsal noradrenergic bundle impair attentional set-shifting in the rat
Tait, D. S., Brown, V. J., Farovik, A., Theobald, D. E., Dalley, J. W., & Robbins, T. W. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05612.x · Cited by 179 · see citing works
Self-citationSerotonin neurons modulate learning rate through uncertainty
Grossman, C. D., Bari, B. A., & Cohen, J. Y. (2022) · Current Biology · doi:10.1016/j.cub.2021.12.006 · Cited by 164 · see citing works
Cools, R., Robinson, O. J., & Sahakian, B. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301598 · Cited by 172 · see citing works
Prefrontal cortex executive processes affected by stress in health and disease
Girotti, M., Adler, S. M., Bulin, S. E., Fucich, E. A., Paredes, D., & Morilak, D. A. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.07.004 · Cited by 176 · see citing works
Serotonin and decision making processes
Homberg, J. R. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.06.001 · Cited by 167 · see citing works
Lapiz-Bluhm, M. D. S., Soto-Piña, A. E., Hensler, J. G., & Morilak, D. A. (2009) · Psychopharmacology · doi:10.1007/s00213-008-1224-6 · Cited by 163 · see citing works
Checa-Ros, A., Jeréz-Calero, A., Molina-Carballo, A., Campoy, C., & Muñoz-Hoyos, A. (2021) · Nutrients · doi:10.3390/nu13010249 · Cited by 164 · see citing works
Neural correlates of cognitive control in gambling disorder: a systematic review of fMRI studies
Moccia, L., Pettorruso, M., De Crescenzo, F., De Risio, L., di Nuzzo, L., Martinotti, G., Bifone, A., Janiri, L., & Di Nicola, M. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.04.025 · Cited by 158 · see citing works
Lee, B., Groman, S., London, E. D., & Jentsch, J. D. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301337 · Cited by 148 · see citing works
Dopamine’s Actions in Primate Prefrontal Cortex: Challenges for Treating Cognitive Disorders
Arnsten, A. F. T., Wang, M., & Paspalas, C. D. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010512 · Cited by 149 · see citing works
Dopamine, but not serotonin, regulates reversal learning in the marmoset caudate nucleus
Clarke, H. F., Hill, G. J., Robbins, T. W., & Roberts, A. C. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5066-10.2011 · Cited by 144 · see citing works
Self-citationBoulougouris, V., & Robbins, T. W. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4312-09.2010 · Cited by 136 · see citing works
van Timmeren, T., Daams, J. G., van Holst, R. J., & Goudriaan, A. E. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.11.022 · Cited by 128 · see citing works
Hains, A. B., & Arnsten, A. F. T. (2008) · Learning & Memory · doi:10.1101/lm.921708 · Cited by 127 · see citing works
Dodds, C. M., Muller, U., Clark, L., van Loon, A., Cools, R., & Robbins, T. W. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1153-08.2008 · Cited by 113 · see citing works
Self-citationObsessive-compulsive disorder: Etiology, neuropathology, and cognitive dysfunction
Jalal, B., Chamberlain, S. R., & Sahakian, B. J. (2023) · Brain and Behavior · doi:10.1002/brb3.3000 · Cited by 111 · see citing works
Boulougouris, V., Castañé, A., & Robbins, T. W. (2009) · Psychopharmacology · doi:10.1007/s00213-008-1341-2 · Cited by 104 · see citing works
Self-citationFreyer, T., Klöppel, S., Tüscher, O., Kordon, A., Zurowski, B., Kuelz, A.-K., Speck, O., Glauche, V., & Voderholzer, U. (2011) · Psychological Medicine · doi:10.1017/s0033291710000309 · Cited by 105 · see citing works
Wallace, A., Pehrson, A. L., Sánchez, C., & Morilak, D. A. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145714000571 · Cited by 97 · see citing works
Rygula, R., Clarke, H. F., Cardinal, R. N., Cockcroft, G. J., Xia, J., Dalley, J. W., Robbins, T. W., & Roberts, A. C. (2015) · Cerebral Cortex · doi:10.1093/cercor/bhu102 · Cited by 85 · see citing works
Self-citationBondi, C. O., Jett, J. D., & Morilak, D. A. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.04.016 · Cited by 88 · see citing works
Besson, M., Pelloux, Y., Dilleen, R., Theobald, D. E., Lyon, A., Belin-Rauscent, A., Robbins, T. W., Dalley, J. W., Everitt, B. J., & Belin, D. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.95 · Cited by 81 · see citing works
Furr, A., Lapiz-Bluhm, M. D., & Morilak, D. A. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711001441 · Cited by 74 · see citing works
Acute stress impairs set-shifting but not reversal learning
Butts, K. A., Floresco, S. B., & Phillips, A. G. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.06.007 · Cited by 77 · see citing works
TAIT, D. S., & BROWN, V. J. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1401.010 · Cited by 75 · see citing works
Danet, M., Lapiz-Bluhm, S., & Morilak, D. A. (2010) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145710000039 · Cited by 63 · see citing works
Langley, C., Armand, S., Luo, Q., Savulich, G., Segerberg, T., Søndergaard, A., Pedersen, E. B., Svart, N., Overgaard-Hansen, O., Johansen, A., et al. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-022-01523-x · Cited by 58 · see citing works
Self-citationImpaired reward learning and intact motivation after serotonin depletion in rats
Izquierdo, A., Carlos, K., Ostrander, S., Rodriguez, D., McCall-Craddolph, A., Yagnik, G., & Zhou, F. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.05.032 · Cited by 59 · see citing works
Brown, H. D., Amodeo, D. A., Sweeney, J. A., & Ragozzino, M. E. (2012) · Journal of Psychopharmacology · doi:10.1177/0269881111430749 · Cited by 56 · see citing works
Clarke, H. F., Cardinal, R. N., Rygula, R., Hong, Y. T., Fryer, T. D., Sawiak, S. J., Ferrari, V., Cockcroft, G., Aigbirhio, F. I., Robbins, T. W., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0718-14.2014 · Cited by 54 · see citing works
Self-citationAthilingam, J. C., Ben-Shalom, R., Keeshen, C. M., Sohal, V. S., & Bender, K. J. (2017) · eLife · doi:10.7554/elife.31991 · Cited by 49 · see citing works
A dimensional approach to modeling symptoms of neuropsychiatric disorders in the marmoset monkey
Oikonomidis, L., Santangelo, A. M., Shiba, Y., Clarke, F. H., Robbins, T. W., & Roberts, A. C. (2017) · Developmental Neurobiology · doi:10.1002/dneu.22446 · Cited by 54 · see citing works
Self-citationThe role of 5-HT2C receptors in touchscreen visual reversal learning in the rat: a cross-site study
Alsiö, J., Nilsson, S. R. O., Gastambide, F., Wang, R. A. H., Dam, S. A., Mar, A. C., Tricklebank, M., & Robbins, T. W. (2015) · Psychopharmacology · doi:10.1007/s00213-015-3963-5 · Cited by 53 · see citing works
Self-citationArnsten, A. F. T., & Wang, M. (2016) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103617 · Cited by 50 · see citing works
Translational Assessments of Reward and Anhedonia: A Tribute to Athina Markou
Der-Avakian, A., & Pizzagalli, D. A. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.02.008 · Cited by 36 · see citing works
Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans
Kanen, J. W., Apergis-Schoute, A. M., Yellowlees, R., Arntz, F. E., van der Flier, F. E., Price, A., Cardinal, R. N., Christmas, D. M., Clark, L., Sahakian, B. J., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01240-9 · Cited by 34 · see citing works
Self-citationBeta-adrenergic antagonist effects on a novel cognitive flexibility task in rodents
Hecht, P. M., Will, M. J., Schachtman, T. R., Welby, L. M., & Beversdorf, D. Q. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.11.041 · Cited by 33 · see citing works
Complementary roles of serotonergic and cholinergic systems in decisions about when to act
Khalighinejad, N., Manohar, S., Husain, M., & Rushworth, M. F. S. (2022) · Current Biology · doi:10.1016/j.cub.2022.01.042 · Cited by 29 · see citing works
Serotonergic neuromodulation of synaptic plasticity
Higa, G. S. V., Viana, F. J. C., Francis-Oliveira, J., Cruvinel, E., Franchin, T. S., Marcourakis, T., Ulrich, H., & De Pasquale, R. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110036 · Cited by 29 · see citing works
A Role for Serotonin in Modulating Opposing Drive and Brake Circuits of Impulsivity
Desrochers, S. S., Spring, M. G., & Nautiyal, K. M. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.791749 · Cited by 29 · see citing works
The Neurochemical Modulation of Prefrontal Control Processes
Robbins, T. W., & Kehagia, A. A. (2017) · The Wiley Handbook of Cognitive Control · doi:10.1002/9781118920497.ch19 · Cited by 4 · see citing works
Self-citation
- Authors
- Clarke, H., Walker, S., Dalley, J., Robbins, T., & Roberts, A.
- Affiliations
- University of Cambridge (GB)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-02-01
- Volume
- 17
- Issue
- 1
- Pages
- 18-27
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2121245502
- Cited by
- 351
- References
- 56
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 11 · 2023: 8 · 2022: 18 · 2021: 16 · 2020: 19 · 2019: 16 · 2018: 14 · 2017: 16 · 2016: 16 · 2015: 23 · 2014: 20 · 2013: 30 · 2012: 15
- FWCI
- 10.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- University of Cambridge
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- cognitive inflexibility, orbitofrontal cortex, set-shifting, selective serotonin reuptake inhibitors, response inhibition, proactive interference, prefrontal cortex, neuropsychiatric disorders
- MeSH terms
- Animals, Avoidance Learning, Behavior, Animal, Brain Chemistry, Callithrix, Cognition, Color, Discrimination Learning, Dopamine, Female, Hydroxydopamines, Hydroxyindoleacetic Acid, Male, Norepinephrine, Photic Stimulation, Psychomotor Performance, Reversal Learning, Reward, Serial Learning, Serotonin, 5,7-Dihydroxytryptamine, Prefrontal Cortex, Serotonin Agents
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
