Self-evaluation in schizophrenia: an fMRI study with implications for the understanding of insight

BMC Psychiatry

Anthony S David²  Michael J Brammer¹  Vincent Giampietro¹  Simon Surguladze²  Nicholas J Bedford² 

[1] Department of Neuroimaging, Institute of Psychiatry, King’s College London, London, UK;Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, UK

关键词: Medial-frontal cortex;    Self-awareness;    fMRI;    Schizophrenia;    Insight;   

Others  :  1124325
DOI  :  10.1186/1471-244X-12-106

 received in 2012-03-06, accepted in 2012-07-30,  发布年份 2012

【 摘 要 】

Background

Lack of insight is a core feature of schizophrenia and is associated with structural brain abnormalities. The functional neuroanatomy of insight has only recently been investigated. When people evaluate their personality traits compared to those of another, activation is seen in central midline structures (CMS) of the brain. This study set out to compare cerebral activation in schizophrenia patients versus controls during a self-evaluation task which included positive and negative traits as well as mental and physical illness terms.

Methods

Eleven schizophrenia patients and 8 healthy controls, matched for age were studied. Insight was assessed using the Schedule for the Assessment of Insight-expanded version (SAI-E). FMRI data were obtained with a 1.5 Tesla GE system and interactions between participant group, self versus other, significant at the cluster level, were recorded.

Results

Significant hypoactivation in the medial superior frontal gyrus (dorsomedial prefrontal cortex) was observed in patients vs. controls during self-evaluation of all traits combined. A second cluster of hypoactivation in the posterior cingulate was also detected. When the response to individual traits was explored, underactivation in other frontal regions plus right inferior parietal lobule emerged and this tended to correlate, albeit weakly with lower insight scores. Further, there were areas of hyperactivation relative to controls in anterior cingulate, frontal and parietal regions (especially precuneus) which showed moderate inverse correlations with insight scores.

Conclusions

We have demonstrated that the CMS, identified as a key system underpinning self-evaluation, is dysfunctional in patients with schizophrenia, particularly dorso-medial PFC. This may have implications for lack of insight in schizophrenia. Hypofunction within the dorsomedial prefrontal region seems to be particularly important although other posterior and lateral cortical regions play a part and may modulate self-evaluative responses depending on the type of trait under consideration.

【 授权许可】

   
2012 Bedford et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]David AS: Insight and Psychosis. Br J Psychiatry 1990, 156:798-808.
• [2]Amador XF, David AS: Insight and psychosis: awareness of illness in schizophrenia and related disorders. 2nd edition. Oxford University Press, Oxford; 2004.
• [3]Osatuke K, Ciesla J, Kasckow JW, Zisook S, Mohamed S: Insight in schizophrenia: a review of etiological models and supporting research. Compr Psychiatry 2008, 49:70-77.
• [4]Mintz AR, Dobson KS, Romney DM: Insight in schizophrenia: a meta-analysis. Schizophr Res 2003, 61:75-88.
• [5]Lincoln TM, Lullmann E, Rief W: Correlates and long-term consequences of poor insight in patients with schizophrenia. A systematic review. Schizophrenia Bulletin 2007, 33(6):1324-1342.
• [6]Wiffen B, Rabinowitz R, Fleischhacker W, David AS: Insight: Demographic differences and associations with 1 year outcome in schizophrenia and schizoaffective disorder. Clin Schizophr Relat Psychoses 2010, 4:169-175.
• [7]Gilleen J, Greenwood K, David AS: In the study of anosognosia. In Anosognosia in schizophrenia and other neuropsychiatric disorders: similarities and differences. Edited by Prigatano GP. Oxford University Press, Oxford; 2009:255-290.
• [8]Prigatano GP: The study of anosognosia. Oxford University Press, New York; 2009.
• [9]Aleman A, Agrawal N, Morgan KD, David AS: Insight in psychosis and neuropsychological function: Meta-analysis. Br J Psychiatry 2006, 189:204-212.
• [10]Lysaker PH, Warman DM, Dimaggio G, Procacci M, LaRocco VA, Clark LK, Dike CA, Nicolo G: Metacognition in schizophrenia: associations with multiple assessments of executive function. J Nerv Ment Dis 2008, 196:384-389.
• [11]Rossell SL, Coakes J, Shapleske J, Woodruff PWR: Insight: its relationship with cognitive function, brain volume and symptoms in schizophrenia. Psychol Med 2003, 33:111-119.
• [12]Morgan KD, Dazzan P, Morgan C, Lappin J, Hutchinson G, Suckling J, Fearon P, Jones PB, Leff J, Murray RM, David AS: Insight, grey matter and cognitive function in first-onset psychosis. Br J Psychiatry 2010, 197:141-148.
• [13]Antonius D, Prudent V, Rebani Y, D'Angelo D, Ardekani BA, Malaspina D, Hoptman MJ: White matter integrity and lack of insight in schizophrenia and schizoaffective disorder. Schizophr Res 2011, 128:76-82.
• [14]Laroi F, Fannemel M, Ronneberg U, Flekkoy K, Opjordsmoen S, Dullerud R, Haakonsen M: Unawareness of illness in chronic schizophrenia and its relationship to structural brain measures and neuropsychological tests. Psychiatry Res 2000, 100:49-58.
• [15]Flashman LA, McAllister TW, Johnson SC, Rick JH, Green RL, Saykin AJ: Specific frontal lobe subregions correlated with unawareness of illness in schizophrenia: a preliminary study. J Neuropsychiatry Clin Neurosci 2001, 13:255-257.
• [16]Buchy L, AdDab’bagh Y, Malla A, Lepage C, Bodnar M, Joober R, Sergerie K, Evans A, Lepage M: Cortical thickness is associated with poor insight in first-episode psychosis. J. Psychiat Res 2010.
• [17]Sapara A, Cooke M, Fannon D, Francis A, Buchanan RW, Anilkumar APP, Barkataki I, Aasen I, Kuipers E, Kumari V: Prefrontal cortex and insight in schizophrenia: A volumetric MRI study. Schizophr Res 2007, 89:22-34.
• [18]Bergé D, Carmona S, Rovira M, Bulbena A, Salgado P, Vilarroya O: Gray matter volume deficits and correlation with insight and negative symptoms in first-psychotic-episode subjects. Acta Psychiatr Scand 2010, 2010:1-9.
• [19]Ha T, Youn T, Ha K, Rho K, Lee J, Kim I, Kim S, Kwon J: Grey matter abnormalities in paranoid schizophrenia and their clinical correlations. Psychiatry Research-Neuroimaging 2004, 132:251-260.
• [20]Cooke MA, Fannon D, Kuipers E, Peters E, Williams SC, Kumari V: Neurological basis of poor insight in psychosis: a voxel-based MRI study. Schizophr Res 2008, 103:40-51.
• [21]Shad MU, Muddasani S, Keshavan MS: Prefrontal subregions and dimensions of insight in first-episode schizophrenia - A pilot study. Psychiatry Res 2006, 146:35-42.
• [22]Bassitt DP, Neto MRL, de Castro CC, Busatto GF: Insight and regional brain volumes in schizophrenia. Eur Arch Psychiatry Clin Neurosci 2007, 257:58-6.
• [23]Shad MU, Muddasani S, Sahni SD, Keshavan MS: Insight and prefrontal cortex in first-episode schizophrenia. Neuroimage 2004, 22:1315-1320.
• [24]Palaniyappan L, Mallikarjun P, Joseph V, Liddle PF: Appreciating symptoms and deficits in schizophrenia: Right posterior insula and poor insight. Prog Neuropsychopharmacol Biol Psychiatry 2011, 2011(35):523-527.
• [25]Saxe R, Offen S: Metacognition and severe adult mental disorders. In Seeing ourselves: what vision can teach us about metacognition. Edited by Dimaggio G, Lysaker PH. Routledge, Hove, East Sussex; 2010:13-30.
• [26]Amodio DM, Frith CD: Meeting of minds: the medial frontal cortex and social cognition. Nat Rev Neurosci 2006, 7:268-277.
• [27]Craik FIM, Moroz TM, Moscovitch M, Stuss DT, Winocur G, Tulving E, Kapur S: In search of the self: A positron emission tomography study. Psychol Sci 1999, 10:26-34.
• [28]Schmitz TW, Kawahara-Baccus TN, Johnson SC: Metacognitive evaluation, self-relevance, and the right prefrontal cortex. Neuroimage 2004, 22:941-947.
• [29]Northoff G, Heinzel AGM, Bermpohl F, Dobrowolny H, Panksepp J: Self-referential processing in our brain - a meta-analysis of imaging studies on the self. Neuroimage 2006, 31:440-457.
• [30]Schmitz TW, Johnson SC: Relevance to self: A brief review and framework of neural systems underlying appraisal. Neuroscience and Biobehavioral Review 2007, 31:585-596.
• [31]Van der Meer L, Costafreda SC, Aleman A, David AS: Self-reflection and the brain: a theoretical review and meta-analysis of neuroimaging studies with implications for schizophrenia. Neuroscience and Biobehavioral Review 2010, 34:935-946.
• [32]Jenkins AC, Mitchell JP: Medial prefrontal cortex subserves diverse forms of self-reflection. Soc Neurosci 2011, 6:211-218.
• [33]Legrand D, Ruby P: What is self-specific? Theoretical investigation and critical review of neuroimaging results. Psychol Rev 2009, 116:252-282.
• [34]Lombardo MV, Chakrabarti B, Bullmore ET, Wheelwright SJ, Sadek SA, Suckling J, Baron-Cohen S: Shared neural circuits for mentalizing about the self and others. J Cogn Neurosci 2009, 22:1623-1635.
• [35]Ochsner KN, Beer JS, Robertson ER, Cooper JC, Gabrieli JD, Kihsltrom JF, D'Esposito M: The neural correlates of direct and reflected self-knowledge. Neuroimage 2005, 28:797-814.
• [36]Gillihan SJ, Farah MJ: Is self special? A critical review of evidence from experimental psychology and cognitive neuroscience. Psychology Bulletin 2005, 131:76-97.
• [37]Heatherton TF, Wyland CL, Macrae CN, Demos KE, Denny BT, Kelley WM: Medial prefrontal activity differentiates self from close others. Soc Cogn Affect Neurosci 2006, 1:18-25.
• [38]Lee K-H, Brown WH, Egleston PN, Green RDJ, Farrow TFD, Hunter MD, Parks RW, Wilkinson ID, Spence SA, Woodruff PWR: A functional magnetic resonance imaging study of social cognition in schizophrenia during an acute episode and after recovery. Am J Psychiatry 2006, 163:1926-1933.
• [39]Murphy ER, Brent BK, Benton M, Pruitt P, Diwadkar V, Rajarethinam RP, Keshavan MS: Differential processing of metacognitive evaluation and the neural circuitry of the self and others in schizophrenia: A pilot study. Schizophr Res 2010, 116:252-258.
• [40]Holt DJ, Cassidy BS, Andrews-Hanna JR, Lee SM, Coombs G, Goff DC, Gabrieli JD, Moran JM: An anterior-to-posterior shift in midline cortical activity in schizophrenia during self-reflection. Biol Psychiatry 2011, 69:415-423.
• [41]Modinos G, Renken R, Ormel J, Aleman A: Self-reflection and the psychosis-prone brain: an fMRI study. Neuropsychology 2011, 25:295-305.
• [42]Schmitz TW, Rowley HA, Kawahara TN, Johnson SC: Neural correlates of self-evaluative accuracy after traumatic brain injury. Neuropsychologia 2006, 44:762-773.
• [43]Kay SR, Fiszbein A, Opler LA: The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987, 13:261-276.
• [44]Sanz M, Constable G, Lopez-Ibor I, Kemp R, David AS: A comparative study of insight scales and their relationship to psychopathological and clinical variables. Psychol Med 1998, 28:437-446.
• [45]Arthumbutt KFJ: Executive control in set switching: Residual switch cost and task-set inhibition. Can J Psychiatry 2000, 54:33-41.
• [46]Wechsler D (Ed): Wechsler Memory Scale-III Technical Manual. The Psychological Corporation, San Antonio, TX; 1997.
• [47]Wechsler D (Ed): Wechsler Abbreviated Scale of Intelligence (WASI) San Antonio. The Psychological Corporation, TX; 1999.
• [48]Brammer MJ, Bullmore ET, Simmons A, Williams SC, Grasby PM, Howard RJ, et al.: Generic brain activation mapping in functional magnetic resonance imaging: A nonparametric approach. Magn Reson Imaging 1997, 15:763-770.
• [49]Bullmore ET, Long C, Suckling J, et al.: Colored noise and computational inference in neurophysiological (fMRI) time series analysis: resampling methods in time and wavelet domains. Hum Brain Mapp 2001, 12:61-78.
• [50]Bullmore ET, Brammer MJ, Rabe-Hesketh S, et al.: Methods for diagnosis and treatment of stimulus correlated motion in generic brain activation studies using fMRI. Hum Brain Mapp 1999, 7:38-48.
• [51]Friman O, Borga P, Lundberg P, Knutsson H: Adaptive analysis of fMRI data. Neuroimage 2003, 19:837-845.
• [52]Talairach J, Tournoux P: Co-Planar Stereotaxic Atlas of the Human Brain. Thieme, Stuttgart New York; 1988.
• [53]Bullmore ET, Suckling J, Overmeyer S, Rabe-Hesketh S, Taylor E, Brammer MJ: Global, voxel and cluster tests, by theory and permutation for a difference between two groups of structural MR images of the brain. IEEE Trans Med Imaging 1999, 18:32-42.
• [54]David AS, Bedford N, Wiffen B, Gilleen J: Failures of metacognition and lack of insight in neuropsychiatric disorders. Philosophical Transactions of the Royal Society B 2012, 267:1379-90.
• [55]Costafreda S, Fu CHY, Lee L, Everitt B, Brammer MJ, David AS: A Systematic review and quantitative appraisal of fMRI studies of verbal fluency: role of the left inferior frontal gyrus. Hum Brain Mapp 2006, 27:799-810.
• [56]Johnson MK, Raye CL, Mitchell KJ, Touryan SR, Greene EJ, Nolen-Hoeksema S: Dissociating medial frontal and posterior cingulate activity during self-reflection. Soc Cogn Affect Neurosci 2006, 1:56-64.
• [57]Michalakeas A, Skoutas C, Charalambous A, Peristeris A, Marinos A, Keramari E: Insight in schizophrenia and mood disorders and its relation to psychopathology. Acta Psychiatric Scandinavica 1994, 90:46-49.
• [58]Varga M, Magnusson A, Flekkoy K, David AS, Opjordsmoen S: Clinical and neuropsychological correlates of insight in schizophrenia and bipolar I disorder: does diagnosis matter? Compr Psychiatry 2007, 28:583-591.
• [59]Fotopoulou A, Pernigo S, Maeda R, Rudd A, Kopelman A: Implicit awareness in anosognosia for hemiplegia: unconscious interference without conscious re-representation. Brain 2010, 133:3564-3577.
• [60]Torrey EF: Schizophrenia and the inferior parietal lobule. Schizophr Res 2007, 97:215-225.
• [61]Bedford N, David A: Poor insight in psychosis: cognitive deficit or bias? Schizophr Bull 2009, 35(suppl 1):281.
• [62]Warman DM, Lysaker PH, Martin JM: Cognitive insight and psychotic disorder: The impact of active delusions. Schizophr Res 2007, 90(1–3):325-333.
• [63]Engh JA, Friis S, Birkenaes A, Jonsdottir H, Ringen P, Ruud T, Sundet KS, Opjordsmoen S, Andreassen OA: Measuring cognitive insight in schizophrenia and bipolar disorder: a comparative study. BMC Psychiatry 2007, 7:71. BioMed Central Full Text
• [64]Lappin JM, Morgan KD, Valmaggia LR, Broome MD, Woolley JB, Johns LC, Tabraham P, Bramon E, McGuire PK: Insight in individuals with an at risk mental state. Schizophr Res 2007, 90:238-244.
• [65]Wiffen BDR, Rabinowitz J, Lex A, David AS: Correlates, change and ‘state or trait’ properties of insight in schizophrenia. Schizophr Res 2010, 122:94-103.
• [66]Pomarol-Clotet E, Canales-Rodríguez EK, Salvador R, Sarró S, Gomar JJ, Vila F, Ortiz-Gil J, Iturria-Medina Y, Capdevila A, McKenna PJ: Medial prefrontal cortex pathology in schizophrenia as revealed by convergent findings from multimodal imaging. Mol Psychiatry 2010, 15:823-830.
• [67]McEvoy JP, Johnson J, Perkins D, Lieberman JA, Hamer RM, Keefe RS, Tohen M, Glick ID, Sharma T: Insight in first-episode psychosis. Psychol Med 2006, 36:1385-1393.
• [68]Parellada M, Boada L, Fraguas D, Reig S, Castro-Fornieles J, Moreno D, Gonzalez-Pinto A, Ptero S, Rapado-Castor M, Rapado-Graell M, Baeza I, Arango C: Trait and state attributes of insight in first episodes of early-onset schizophrenia and other psychoses: a 2-year longitudinal study. Schizophr Bull 2011, 37:38-51.
• [69]Surguladze S, Chu EM, Marshall N, Evans A, Anilkumar APP, Timehin C, McDonald C, Ecker C, Phillips ML, David AS: Emotion processing in schizophrenia: fMRI study of patients treated with risperidone long-acting injections or conventional depot medication. J Psychopharmacol 2011, 25:722-733.
• [70]Cooke MA, Peters ER, Kuipers E, Kumari V: Disease, deficit or denial? Models of poor insight in psychosis. Acta Psychiatr Scand 2005, 112:4-17.