Professor Paul Fletcher

Paul Fletcher

University position

Bernard Wolfe Professor of Health Neuroscience

Departments

Department of Psychiatry

Institutes

Behavioural and Clinical Neuroscience Institute

Home page

http://www.psychiatry.cam.ac.uk

Research Theme

Cognitive and Behavioural Neuroscience

Interests

I am interested in psychosis. I agree with the long tradition of clinical psychiatric research which suggests that, during a psychotic illness, the world is a strange place because strange associations are formed and inconsequential stimuli are assigned undue weight. This can be extremely unpleasant. I think that, if we can understand the brain basis for how associations are made and how we come to think of particular environmental stimuli as important, then perhaps we can apply this to understanding psychotic symptoms such as delusions, hallucinations and thought disorder.

I use combined functional neuroimaging and pharmacological experiments together with studies with patients in order to explore the extent to which such symptoms may be related to deficits in basic learning processes.

Research Focus

Keywords

Psychosis

Schizophrenia

Learning

Memory

Clinical conditions

Schizophrenia

Equipment

Neuropsychological testing

Collaborators

Cambridge

Sergio Arana

Ed Bullmore

Phil Corlett

Sanne de Wit

Jon McCabe

Graham Murray

Jon Simons

United Kingdom

Chris Frith Web: http://www.fil.ion.ucl.ac.uk

International

Aaron Mishara Web: http://www.thechicagoschool.edu/content...

Key publications

Fletcher PC, Honey GD (2006), “Schizophrenia, ketamine and cannabis: evidence of overlapping memory deficits” Trends in the Cognitive Sciences 10(4):167-174 Details

Pomarol-Clotet E, Honey GD, Murray GK, Corlett PR, Absalom AR, Lee M, McKenna PJ, Bullmore ET, Fletcher PC (2006), “Physiological effects of ketamine in healthy volunteers: Phenomenological study” British Journal of Psychiatry 189:173-179 Details

Fletcher PC, Zafiris O, Frith CD, Honey RAE, P Corlett, Zilles K, Fink GR (2005), “On the benefits of not trying: brain activity and connectivity reflecting the interactions of explicit and implicit sequence learning” Cerebral Cortex 15:1002-1015

Publications

2010

Corlett PR, Honey GD, Krystal JH, Fletcher PC (2010), “Glutamatergic Model Psychoses: Prediction Error, Learning, and Inference.” Neuropsychopharmacology Details

Corlett PR, Taylor JR, Wang XJ, Fletcher PC, Krystal JH (2010), “Toward a neurobiology of delusions.” Prog Neurobiol Details

Craig MC, Brammer M, Maki PM, Fletcher PC, Daly EM, Rymer J, Giampietro V, Picchioni M, Stahl D, Murphy DG (2010), “The interactive effect of acute ovarian suppression and the cholinergic system on visuospatial working memory in young women.” Psychoneuroendocrinology 35(7):987-1000 Details

Liao Y, Tang J, Ma M, Wu Z, Yang M, Wang X, Liu T, Chen X, Fletcher PC, Hao W (2010), “Frontal white matter abnormalities following chronic ketamine use: a diffusion tensor imaging study.” Brain 133(Pt 7):2115-22 Details

Morcom AM, Bullmore ET, Huppert FA, Lennox B, Praseedom A, Linnington H, Fletcher PC (2010), “Memory encoding and dopamine in the aging brain: a psychopharmacological neuroimaging study.” Cereb Cortex 20(3):743-57 Details

Murray GK, Corlett PR, Fletcher PC (2010), “The neural underpinnings of associative learning in health and psychosis: how can performance be preserved when brain responses are abnormal?” Schizophr Bull 36(3):465-71 Details

Teufel C, Fletcher PC, Davis G (2010), “Seeing other minds: attributed mental states influence perception.” Trends Cogn Sci 14(8):376-82 Details

2009

Bhattacharyya S, Fusar-Poli P, Borgwardt S, Martin-Santos R, Nosarti C, O'Carroll C, Allen P, Seal ML, Fletcher PC, Crippa JA, Giampietro V, Mechelli A, Atakan Z, McGuire P (2009), “Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis.” Arch Gen Psychiatry 66(4):442-51 Details

Corlett PR, Frith CD, Fletcher PC (2009), “From drugs to deprivation: a Bayesian framework for understanding models of psychosis.” Psychopharmacology (Berl) 206(4):515-30 Details

Corlett PR, Krystal JH, Taylor JR, Fletcher PC (2009), “Why do delusions persist?” Front Hum Neurosci 3:12 Details

Corlett PR, Simons JS, Pigott JS, Gardner JM, Murray GK, Krystal JH, Fletcher PC (2009), “Illusions and delusions: relating experimentally-induced false memories to anomalous experiences and ideas.” Front Behav Neurosci 3:53 Details

Craig MC, Fletcher PC, Daly EM, Rymer J, Brammer M, Giampietro V, Stahl D, Maki PM, Murphy DG (2009), “The interactive effect of the cholinergic system and acute ovarian suppression on the brain: an fMRI study.” Horm Behav 55(1):41-9 Details

de Wit S, Corlett PR, Aitken MR, Dickinson A, Fletcher PC (2009), “Differential engagement of the ventromedial prefrontal cortex by goal-directed and habitual behavior toward food pictures in humans.” J Neurosci 29(36):11330-8 Details

Fletcher PC, Frith CD (2009), “Perceiving is believing: a Bayesian approach to explaining the positive symptoms of schizophrenia.” Nat Rev Neurosci 10(1):48-58 Details

2008

Craig MC, Fletcher PC, Daly EM, Picchioni MM, Brammer M, Giampietro V, Rymer J, McGuire PK, Maki PM, Murphy DG (2008), “A study of visuospatial working memory pre- and post-Gonadotropin Hormone Releasing Hormone agonists (GnRHa) in young women.” Horm Behav 54(1):47-59 Details

Craig MC, Fletcher PC, Daly EM, Rymer J, Brammer M, Giampietro V, Maki PM, Murphy DG (2008), “Reversibility of the effects of acute ovarian hormone suppression on verbal memory and prefrontal function in pre-menopausal women.” Psychoneuroendocrinology 33(10):1426-31 Details

Craig MC, Fletcher PC, Daly EM, Rymer J, Brammer M, Giampietro V, Murphy DG (2008), “Physiological variation in estradiol and brain function: a functional magnetic resonance imaging study of verbal memory across the follicular phase of the menstrual cycle.” Horm Behav 53(4):503-8 Details

Honey GD, Corlett PR, Absalom AR, Lee M, Pomarol-Clotet E, Murray GK, McKenna PJ, Bullmore ET, Menon DK, Fletcher PC (2008), “Individual differences in psychotic effects of ketamine are predicted by brain function measured under placebo.” J Neurosci 28(25):6295-303 Details

Murray GK, Cheng F, Clark L, Barnett JH, Blackwell AD, Fletcher PC, Robbins TW, Bullmore ET, Jones PB (2008), “Reinforcement and reversal learning in first-episode psychosis.” Schizophr Bull 34(5):848-55 Details

Murray GK, Corlett PR, Clark L, Pessiglione M, Blackwell AD, Honey G, Jones PB, Bullmore ET, Robbins TW, Fletcher PC (2008), “Substantia nigra/ventral tegmental reward prediction error disruption in psychosis.” Mol Psychiatry 13(3):239, 267-76 Details

Poldrack RA, Fletcher PC, Henson RN, Worsley KJ, Brett M, Nichols TE (2008), “Guidelines for reporting an fMRI study.” Neuroimage 40(2):409-14 Details

Simons JS, Henson RN, Gilbert SJ, Fletcher PC (2008), “Separable forms of reality monitoring supported by anterior prefrontal cortex.” J Cogn Neurosci 20(3):447-57 Details

Simons JS, Peers PV, Hwang DY, Ally BA, Fletcher PC, Budson AE (2008), “Is the parietal lobe necessary for recollection in humans?” Neuropsychologia 46(4):1185-91 Details

2007

Absalom AR, Lee M, Menon DK, Sharar SR, De Smet T, Halliday J, Ogden M, Corlett P, Honey GD, Fletcher PC (2007), “Predictive performance of the Domino, Hijazi, and Clements models during low-dose target-controlled ketamine infusions in healthy volunteers.” Br J Anaesth 98(5):615-23 Details

Corlett PR, Honey GD, Fletcher PC (2007), “From prediction error to psychosis: ketamine as a pharmacological model of delusions.” J Psychopharmacol 21(3):238-52 Details

Corlett PR, Murray GK, Honey GD, Aitken MR, Shanks DR, Robbins TW, Bullmore ET, Dickinson A, Fletcher PC (2007), “Disrupted prediction-error signal in psychosis: evidence for an associative account of delusions.” Brain 130(Pt 9):2387-400 Details

Craig MC, Fletcher PC, Daly EM, Rymer J, Cutter WJ, Brammer M, Giampietro V, Wickham H, Maki PM, Murphy DG (2007), “Gonadotropin hormone releasing hormone agonists alter prefrontal function during verbal encoding in young women.” Psychoneuroendocrinology 32(8-10):1116-27 Details

Farooqi IS, Bullmore E, Keogh J, Gillard J, O'Rahilly S, Fletcher PC (2007), “Leptin regulates striatal regions and human eating behavior.” Science 317(5843):1355 Details

Morcom AM, Fletcher PC (2007), “Does the brain have a baseline? Why we should be resisting a rest.” Neuroimage 37(4):1073-82 Details

Morcom AM, Fletcher PC (2007), “Does the brain have a baseline? Why we should be resisting a rest.” Neuroimage 37(4):1073-1082 Details

Tobler PN, Fletcher PC, Bullmore ET, Schultz W (2007), “Learning-related human brain activations reflecting individual finances.” Neuron 54(1):167-75 Details

2006

Corlett PR, Honey GD, Aitken MR, Dickinson A, Shanks DR, Absalom AR, Lee M, Pomarol-Clotet E, Murray GK, McKenna PJ, Robbins TW, Bullmore ET, Fletcher PC (2006), “Frontal responses during learning predict vulnerability to the psychotogenic effects of ketamine: linking cognition, brain activity, and psychosis.” Arch Gen Psychiatry 63(6):611-21 Details

Ersche KD, Fletcher PC, Roiser JP, Fryer TD, London M, Robbins TW, Sahakian BJ (2006), “Differences in orbitofrontal activation during decision-making between methadone-maintained opiate users, heroin users and healthy volunteers.” Psychopharmacology (Berl) 188(3):364-73 Details

Honey GD, Fletcher PC (2006), “Investigating principles of human brain function underlying working memory: what insights from schizophrenia?” Neuroscience 139(1):59-71 Details

Honey GD, O'loughlin C, Turner DC, Pomarol-Clotet E, Corlett PR, Fletcher PC (2006), “The effects of a subpsychotic dose of ketamine on recognition and source memory for agency: implications for pharmacological modelling of core symptoms of schizophrenia.” Neuropsychopharmacology 31(2):413-23 Details

Müller U, Fletcher PC, Steinberg H (2006), “The origin of pharmacopsychology: Emil Kraepelin's experiments in Leipzig, Dorpat and Heidelberg (1882-1892).” Psychopharmacology (Berl) 184(2):131-8 Details

Parthasarathi UD, Harrower T, Tempest M, Hodges JR, Walsh C, McKenna PJ, Fletcher PC (2006), “Psychiatric presentation of voltage-gated potassium channel antibody-associated encephalopathy. Case report.” Br J Psychiatry 189:182-3 Details

2005

Ersche KD, Fletcher PC, Lewis SJ, Clark L, Stocks-Gee G, London M, Deakin JB, Robbins TW, Sahakian BJ (2005), “Abnormal frontal activations related to decision-making in current and former amphetamine and opiate dependent individuals.” Psychopharmacology (Berl) 180(4):612-23 Details

Fletcher PC, Zafiris O, Frith CD, Honey RA, Corlett PR, Zilles K, Fink GR (2005), “On the benefits of not trying: brain activity and connectivity reflecting the interactions of explicit and implicit sequence learning.” Cereb Cortex 15(7):1002-15 Details

Honey GD, Honey RA, O'Loughlin C, Sharar SR, Kumaran D, Suckling J, Menon DK, Sleator C, Bullmore ET, Fletcher PC (2005), “Ketamine disrupts frontal and hippocampal contribution to encoding and retrieval of episodic memory: an fMRI study.” Cereb Cortex 15(6):749-59 Details

Honey GD, Honey RA, Sharar SR, Turner DC, Pomarol-Clotet E, Kumaran D, Simons JS, Hu X, Rugg MD, Bullmore ET, Fletcher PC (2005), “Impairment of specific episodic memory processes by sub-psychotic doses of ketamine: the effects of levels of processing at encoding and of the subsequent retrieval task.” Psychopharmacology (Berl) 181(3):445-57 Details

Honey GD, Pomarol-Clotet E, Corlett PR, Honey RA, McKenna PJ, Bullmore ET, Fletcher PC (2005), “Functional dysconnectivity in schizophrenia associated with attentional modulation of motor function.” Brain 128(Pt 11):2597-611 Details

Simons JS, Gilbert SJ, Owen AM, Fletcher PC, Burgess PW (2005), “Distinct roles for lateral and medial anterior prefrontal cortex in contextual recollection.” J Neurophysiol 94(1):813-20 Details

Simons JS, Owen AM, Fletcher PC, Burgess PW (2005), “Anterior prefrontal cortex and the recollection of contextual information.” Neuropsychologia 43(12):1774-83 Details

Stamatakis EA, Marslen-Wilson WD, Tyler LK, Fletcher PC (2005), “Cingulate control of fronto-temporal integration reflects linguistic demands: a three-way interaction in functional connectivity.” Neuroimage 28(1):115-21 Details

2004

Bernard FA, Bullmore ET, Graham KS, Thompson SA, Hodges JR, Fletcher PC (2004), “The hippocampal region is involved in successful recognition of both remote and recent famous faces.” Neuroimage 22(4):1704-14 Details

Corlett PR, Aitken MR, Dickinson A, Shanks DR, Honey GD, Honey RA, Robbins TW, Bullmore ET, Fletcher PC (2004), “Prediction error during retrospective revaluation of causal associations in humans: fMRI evidence in favor of an associative model of learning.” Neuron 44(5):877-88 Details

Fletcher PC (2004), “Functional neuroimaging of psychiatric disorders: exploring hidden behaviour.” Psychol Med 34(4):577-81 Details

Fletcher PC (2004), “Functional neuroimaging of schizophrenia: from a genetic predisposition to the emergence of symptoms.” Brain 127(Pt 3):457-9 Details

Fletcher PC, Clarke J (2004), “The use of complementary and alternative medicine among pediatric patients.” Cancer Nurs 27(2):93-9 Details

Honey RA, Honey GD, O'Loughlin C, Sharar SR, Kumaran D, Bullmore ET, Menon DK, Donovan T, Lupson VC, Bisbrown-Chippendale R, Fletcher PC (2004), “Acute ketamine administration alters the brain responses to executive demands in a verbal working memory task: an FMRI study.” Neuropsychopharmacology 29(6):1203-14 Details

Turner DC, Aitken MR, Shanks DR, Sahakian BJ, Robbins TW, Schwarzbauer C, Fletcher PC (2004), “The role of the lateral frontal cortex in causal associative learning: exploring preventative and super-learning.” Cereb Cortex 14(8):872-80 Details

2003

Aron AR, Fletcher PC, Bullmore ET, Sahakian BJ, Robbins TW (2003), “Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans.” Nat Neurosci 6(2):115-6 Details

Aron AR, Schlaghecken F, Fletcher PC, Bullmore ET, Eimer M, Barker R, Sahakian BJ, Robbins TW (2003), “Inhibition of subliminally primed responses is mediated by the caudate and thalamus: evidence from functional MRI and Huntington's disease.” Brain 126(Pt 3):713-23 Details

Fletcher PC, Stephenson CM, Carpenter TA, Donovan T, Bullmorel ET (2003), “Regional brain activations predicting subsequent memory success: an event-related fMRI study of the influence of encoding tasks.” Cortex 39(4-5):1009-26 Details

Honey GD, Suckling J, Zelaya F, Long C, Routledge C, Jackson S, Ng V, Fletcher PC, Williams SC, Brown J, Bullmore ET (2003), “Dopaminergic drug effects on physiological connectivity in a human cortico-striato-thalamic system.” Brain 126(Pt 8):1767-81 Details

Honey RA, Turner DC, Honey GD, Sharar SR, Kumaran D, Pomarol-Clotet E, McKenna P, Sahakian BJ, Robbins TW, Fletcher PC (2003), “Subdissociative dose ketamine produces a deficit in manipulation but not maintenance of the contents of working memory.” Neuropsychopharmacology 28(11):2037-44 Details

2002

Fletcher PC, Palomero-Gallagher N, Zafiris O, Fink GR, Tyler LK, Zilles K (2002), “The influence of explicit instructions and stimulus material on lateral frontal responses to an encoding task.” Neuroimage 17(2):780-91 Details

Honey GD, Fletcher PC, Bullmore ET (2002), “Functional brain mapping of psychopathology.” J Neurol Neurosurg Psychiatry 72(4):432-9 Details

2001

Fletcher PC, Anderson JM, Shanks DR, Honey R, Carpenter TA, Donovan T, Papadakis N, Bullmore ET (2001), “Responses of human frontal cortex to surprising events are predicted by formal associative learning theory.” Nat Neurosci 4(10):1043-8 Details

Fletcher PC, Henson RN (2001), “Frontal lobes and human memory: insights from functional neuroimaging.” Brain 124(Pt 5):849-81 Details

Fletcher PC, Hirdes JP (2001), “Assessing the health and functional status of older women with breast cancer using the Minimum Data Set-Home Care (MDS-HC).” Can J Public Health 92(6):457-9 Details

Rubinsztein JS, Fletcher PC, Rogers RD, Ho LW, Aigbirhio FI, Paykel ES, Robbins TW, Sahakian BJ (2001), “Decision-making in mania: a PET study.” Brain 124(Pt 12):2550-63 Details

2000

Allan K, Dolan RJ, Fletcher PC, Rugg MD (2000), “The role of the right anterior prefrontal cortex in episodic retrieval.” Neuroimage 11(3):217-27 Details

Fletcher PC, Shallice T, Dolan RJ (2000), “"Sculpting the response space"--an account of left prefrontal activation at encoding.” Neuroimage 12(4):404-17 Details

Gallagher HL, Happé F, Brunswick N, Fletcher PC, Frith U, Frith CD (2000), “Reading the mind in cartoons and stories: an fMRI study of 'theory of mind' in verbal and nonverbal tasks.” Neuropsychologia 38(1):11-21 Details

1999

Dolan RJ, Fletcher PC, McKenna P, Friston KJ, Frith CD (1999), “Abnormal neural integration related to cognition in schizophrenia.” Acta Psychiatr Scand Suppl 395:58-67 Details

Fletcher PC, Dolan RJ (1999), “Right prefrontal cortex responds to item familiarity during a memory encoding task.” Memory 7(5-6):703-13 Details

Rugg MD, Fletcher PC, Chua PM, Dolan RJ (1999), “The role of the prefrontal cortex in recognition memory and memory for source: an fMRI study.” Neuroimage 10(5):520-9 Details

Strange BA, Fletcher PC, Henson RN, Friston KJ, Dolan RJ (1999), “Segregating the functions of human hippocampus.” Proc Natl Acad Sci U S A 96(7):4034-9 Details

1998

Fletcher PC, McKenna PJ, Frith CD, Grasby PM, Friston KJ, Dolan RJ (1998), “Brain activations in schizophrenia during a graded memory task studied with functional neuroimaging.” Arch Gen Psychiatry 55(11):1001-8 Details

Fletcher PC, Shallice T, Dolan RJ (1998), “The functional roles of prefrontal cortex in episodic memory. I. Encoding.” Brain 121 ( Pt 7):1239-48 Details

Fletcher PC, Shallice T, Frith CD, Frackowiak RS, Dolan RJ (1998), “The functional roles of prefrontal cortex in episodic memory. II. Retrieval.” Brain 121 ( Pt 7):1249-56 Details

Rugg MD, Fletcher PC, Allan K, Frith CD, Frackowiak RS, Dolan RJ (1998), “Neural correlates of memory retrieval during recognition memory and cued recall.” Neuroimage 8(3):262-73 Details

Rugg MD, Walla P, Schloerscheidt AM, Fletcher PC, Frith CD, Dolan RJ (1998), “Neural correlates of depth of processing effects on recollection: evidence from brain potentials and positron emission tomography.” Exp Brain Res 123(1-2):18-23 Details

1997

Dolan RJ, Fletcher PC (1997), “Dissociating prefrontal and hippocampal function in episodic memory encoding.” Nature 388(6642):582-5 Details

Fletcher PC, Frith CD, Rugg MD (1997), “The functional neuroanatomy of episodic memory.” Trends Neurosci 20(5):213-8 Details

Rugg MD, Fletcher PC, Frith CD, Frackowiak RS, Dolan RJ (1997), “Brain regions supporting intentional and incidental memory: a PET study.” Neuroreport 8(5):1283-7 Details

1996

Fletcher PC, Dolan RJ, Shallice T, Frith CD, Frackowiak RS, Friston KJ (1996), “Is multivariate analysis of PET data more revealing than the univariate approach? Evidence from a study of episodic memory retrieval.” Neuroimage 3(3 Pt 1):209-15 Details

Fletcher PC, Frith CD, Grasby PM, Friston KJ, Dolan RJ (1996), “Local and distributed effects of apomorphine on fronto-temporal function in acute unmedicated schizophrenia.” J Neurosci 16(21):7055-62 Details

Fletcher PC, Shallice T, Frith CD, Frackowiak RS, Dolan RJ (1996), “Brain activity during memory retrieval. The influence of imagery and semantic cueing.” Brain 119 ( Pt 5):1587-96 Details

Rugg MD, Fletcher PC, Frith CD, Frackowiak RS, Dolan RJ (1996), “Differential activation of the prefrontal cortex in successful and unsuccessful memory retrieval.” Brain 119 ( Pt 6):2073-83 Details

1995

Fletcher PC, Dolan RJ, Frith CD (1995), “The functional anatomy of memory.” Experientia 51(12):1197-207 Details

Fletcher PC, Frith CD, Baker SC, Shallice T, Frackowiak RS, Dolan RJ (1995), “The mind's eye--precuneus activation in memory-related imagery.” Neuroimage 2(3):195-200 Details

Fletcher PC, Frith CD, Grasby PM, Shallice T, Frackowiak RS, Dolan RJ (1995), “Brain systems for encoding and retrieval of auditory-verbal memory. An in vivo study in humans.” Brain 118 ( Pt 2):401-16 Details

Fletcher PC, Happé F, Frith U, Baker SC, Dolan RJ, Frackowiak RS, Frith CD (1995), “Other minds in the brain: a functional imaging study of "theory of mind" in story comprehension.” Cognition 57(2):109-28 Details

1994

Grasby PM, Frith CD, Friston KJ, Simpson J, Fletcher PC, Frackowiak RS, Dolan RJ (1994), “A graded task approach to the functional mapping of brain areas implicated in auditory-verbal memory.” Brain 117 ( Pt 6):1271-82 Details

Shallice T, Fletcher P, Frith CD, Grasby P, Frackowiak RS, Dolan RJ (1994), “Brain regions associated with acquisition and retrieval of verbal episodic memory.” Nature 368(6472):633-5 Details