Background: The nature of the alteration of the response to cognitive tasks in first-episode psychosis (FEP) still awaits clarification. We used activation likelihood estimation, an increasingly used method in evaluating normal and pathological brain function, to identify activation changes in functional magnetic resonance imaging (fMRI) studies of FEP during attentional and memory tasks. Methods: We included 11 peer-reviewed fMRI studies assessing FEP patients versus healthy controls (HCs) during performance of attentional and memory tasks. Results: Our database comprised 290 patients with FEP, matched with 316 HCs. Between-group analyses showed that HCs, compared to FEP patients, exhibited hyperactivation of the right middle frontal gyrus (Brodmann area, BA, 9), right inferior parietal lobule (BA 40), and right insula (BA 13) during attentional task performances and hyperactivation of the left insula (BA 13) during memory task performances. Conclusions: Right frontal, parietal, and insular dysfunction during attentional task performance and left insular dysfunction during memory task performance are significant neural functional FEP correlates.

Baldwin P, Browne D, Scully PJ, Quinn JF, Morgan MG, Kinsella A, Owens JM, Russell V, O'Callaghan E, Waddington JL: Epidemiology of first-episode psychosis: illustrating the challenges across diagnostic boundaries through the Cavan-Monaghan study at 8 years. Schizophr Bull 2005;31:624-638.
Radua J, Borgwardt S, Crescini A, Mataix-Cols D, Meyer-Lindenberg A, McGuire PK, Fusar-Poli P: Multimodal meta-analysis of structural and functional brain changes in first episode psychosis and the effects of antipsychotic medication. Neurosci Biobehav Rev 2012;36:2325-2333.
Vita A, De Peri L, Deste G, Sacchetti E: Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies. Transl Psychiatry 2012;2:e190, erratum in Transl Psychiatry 2013;3:e275.
Fox PT, Laird AR, Lancaster JL: Coordinate-based voxel-wise meta-analysis: dividends of spatial normalization. Report of a virtual workshop. Hum Brain Mapp 2005;25:1-5.
Laird AR, Fox PM, Price CJ, Glahn DC, Uecker AM, Lancaster JL, Turkeltaub PE, Kochunov P, Fox PT: ALE meta-analysis: controlling the false discovery rate and performing statistical contrasts. Hum Brain Mapp 2005;25:155-164.
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 2010;8:336-341, erratum in Int J Surg 2010;8:658.
Collins DL, Zijdenbos AP, Kollokian V, Sled JG, Kabani NJ, Holmes CJ, Evans AC: Design and construction of a realistic digital brain phantom. IEEE Trans Med Imaging 1998;17:463-468.
Talairach J, Tournoux P: Co-Planar Stereotactic Atlas of Human Brain. New York, Thieme Medical Publishers, 1998.
Tan HY, Choo WC, Fones CS, Chee MW: fMRI study of maintenance and manipulation processes within working memory in first-episode schizophrenia. Am J Psychiatry 2005;162:1849-1858.
Achim AM, Bertrand MC, Sutton H, Montoya A, Czechowska Y, Malla AK, Joober R, Pruessner JC, Lepage M: Selective abnormal modulation of hippocampal activity during memory formation in first-episode psychosis. Arch Gen Psychiatry 2007;64:999-1014.
Schneider F, Habel U, Reske M, Kellermann T, Stöcker T, Shah NJ, Zilles K, Braus DF, Schmitt A, Schlösser R, Wagner M, Frommann I, Kircher T, Rapp A, Meisenzahl E, Ufer S, Ruhrmann S, Thienel R, Sauer H, Henn FA, Gaebel W: Neural correlates of working memory dysfunction in first-episode schizophrenia patients: an fMRI multi-center study. Schizophr Res 2007;89:198-210.
Yoon JH, Minzenberg MJ, Ursu S, Ryan Walter BS, Wendelken C, Ragland JD, Carter CS: Association of dorsolateral prefrontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: relationship with impaired cognition, behavioral disorganization, and global function. Am J Psychiatry 2008;165:1006-1014, erratum in Am J Psychiatry 2008;165:1359.
Woodward ND, Waldie B, Rogers B, Tibbo P, Seres P, Purdon SE: Abnormal prefrontal cortical activity and connectivity during response selection in first episode psychosis, chronic schizophrenia, and unaffected siblings of individuals with schizophrenia. Schizophr Res 2009;109:182-190.
Nejad AB, Ebdrup BH, Siebner HR, Rasmussen H, Aggernæs B, Glenthøj BY, Baaré WF: Impaired temporoparietal deactivation with working memory load in antipsychotic-naïve patients with first-episode schizophrenia. World J Biol Psychiatry 2011;12:271-281.
Guerrero-Pedraza A, McKenna PJ, Gomar JJ, Sarró S, Salvador R, Amann B, Carrión MI, Landin-Romero R, Blanch J, Pomarol-Clotet E: First-episode psychosis is characterized by failure of deactivation but not by hypo- or hyperfrontality. Psychol Med 2012;42:73-84.
Smieskova R, Allen P, Simon A, Aston J, Bendfeldt K, Drewe J, Gruber K, Gschwandtner U, Klarhoefer M, Lenz C, Scheffler K, Stieglitz RD, Radue EW, McGuire P, Riecher-Rössler A, Borgwardt SJ: Different duration of at-risk mental state associated with neurofunctional abnormalities. A multimodal imaging study. Hum Brain Mapp 2012;33:2281-2294.
Lesh TA, Westphal AJ, Niendam TA, Yoon JH, Minzenberg MJ, Ragland JD, Solomon M, Carter CS: Proactive and reactive cognitive control and dorsolateral prefrontal cortex dysfunction in first episode schizophrenia. Neuroimage Clin 2013;2:590-599.
Niendam TA, Lesh TA, Yoon J, Westphal AJ, Hutchison N, Daniel Ragland J, Solomon M, Minzenberg M, Carter CS: Impaired context processing as a potential marker of psychosis risk state. Psychiatry Res 2014;221:13-20.
Chan RC, Huang J, Zhao Q, Wang Y, Lai YY, Hong N, Shum DH, Cheung EF, Yu X, Dazzan P: Prefrontal cortex connectivity dysfunction in performing the Fist-Edge-Palm task in patients with first-episode schizophrenia and non-psychotic first-degree relatives. Neuroimage Clin 2015;9:411-417.
Eickhoff SB, Bzdok D, Laird AR, Kurth F, Fox PT: Activation likelihood estimation meta-analysis revisited. Neuroimage 2012;59:2349-2361.
Turkeltaub PE, Eickhoff SB, Laird AR, Fox M, Wiener M, Fox P: Minimizing within-experiment and within-group effects in activation likelihood estimation meta-analyses. Hum Brain Mapp 2012;33:1-13.
Fuster JM: The Prefrontal Cortex, ed 5. London, Academic Press, 2015.
Fusar-Poli P, Borgwardt S, Crescini A, Deste G, Kempton MJ, Lawrie S, Mc Guire P, Sacchetti E: Neuroanatomy of vulnerability to psychosis: a voxel-based meta-analysis. Neurosci Biobehav Rev 2011;35:1175-1185.
Shad MU, Muddasani S, Prasad K, Sweeney JA, Keshavan MS: Insight and prefrontal cortex in first-episode Schizophrenia. Neuroimage 2004;22:1315-1320.
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.
Ferri F, Salone A, Ebisch SJ, De Berardis D, Romani GL, Ferro FM, Gallese V: Action verb understanding in first-episode schizophrenia: is there evidence for a simulation deficit? Neuropsychologia 2012;50:988-996.
Duan HF, Gan JL, Yang JM, Cheng ZX, Gao CY, Shi ZJ, Zhu XQ, Liang XJ, Zhao LM: A longitudinal study on intrinsic connectivity of hippocampus associated with positive symptom in first-episode schizophrenia. Behav Brain Res 2015;283:78-86.
Yoon YB, Yun JY, Jung WH, Cho KI, Kim SN, Lee TY, Park HY, Kwon JS: Altered fronto-temporal functional connectivity in individuals at ultra-high-risk of developing psychosis. PLoS One 2015;10:e0135347.
Schmidt A, Smieskova R, Simon A, Allen P, Fusar-Poli P, McGuire PK, Bendfeldt K, Aston J, Lang UE, Walter M, Radue EW, Riecher-Rössler A, Borgwardt SJ: Abnormal effective connectivity and psychopathological symptoms in the psychosis high-risk state. J Psychiatry Neurosci 2014;39:239-248.
Mendrek A, Laurens KR, Kiehl KA, Ngan ET, Stip E, Liddle PF: Changes in distributed neural circuitry function in patients with first-episode schizophrenia. Br J Psychiatry 2004;185:205-214.
Smieskova R, Roiser JP, Chaddock CA, Schmidt A, Harrisberger F, Bendfeldt K, Simon A, Walter A, Fusar-Poli P, McGuire PK, Lang UE, Riecher-Rössler A, Borgwardt S: Modulation of motivational salience processing during the early stages of psychosis. Schizophr Res 2015;166:17-23.
Li F, Lui S, Yao L, Hu J, Lv P, Huang X, Mechelli A, Sweeney JA, Gong Q: Longitudinal changes in resting-state cerebral activity in patients with first-episode schizophrenia: a 1-year follow-up functional MR imaging study. Radiology 2016;279:867-875.
Sasabayashi D, Takayanagi Y, Nishiyama S, Takahashi T, Furuichi A, Kido M, Nishikawa Y, Nakamura M, Noguchi K, Suzuki M: Increased frontal gyrification negatively correlates with executive function in patients with first-episode schizophrenia. Cereb Cortex 2016, Epub ahead of print.
Thakral PP, Slotnick SD: The role of parietal cortex during sustained visual spatial attention. Brain Res 2009;1302:157-166.
Kubicki M, Shenton ME, Salisbury DF, Hirayasu Y, Kasai K, Kikinis R, Jolesz FA, McCarley RW: Voxel-based morphometric analysis of gray matter in first episode schizophrenia. Neuroimage 2002;17:1711-1719.
Schaufelberger MS, Duran FL, Lappin JM, Scazufca M, Amaro E Jr, Leite CC, de Castro CC, Murray RM, McGuire PK, Menezes PR, Busatto GF: Grey matter abnormalities in Brazilians with first-episode psychosis. Br J Psychiatry Suppl 2007;51:s117-s122.
Morgan KD, Dazzan P, Orr KG, Hutchinson G, Chitnis X, Suckling J, Lythgoe D, Pollock SJ, Rossell S, Shapleske J, Fearon P, Morgan C, David A, McGuire PK, Jones PB, Leff J, Murray RM: Grey matter abnormalities in first-episode schizophrenia and affective psychosis. Br J Psychiatry Suppl 2007;51:s111-s116.
De Castro-Manglano P, Mechelli A, Soutullo C, Landecho I, Gimenez-Amaya JM, Ortuño F, McGuire P: Structural brain abnormalities in first-episode psychosis: differences between affective psychoses and schizophrenia and relationship to clinical outcome. Bipolar Disord 2011;13:545-555.
Fusar-Poli P, Smieskova R, Serafini G, Politi P, Borgwardt S: Neuroanatomical markers of genetic liability to psychosis and first episode psychosis: a voxelwise meta-analytical comparison. World J Biol Psychiatry 2014;15:219-228.
Tordesillas-Gutierrez D, Koutsouleris N, Roiz-Santiañez R, Meisenzahl E, Ayesa-Arriola R, Marco de Lucas E, Soriano-Mas C, Suarez-Pinilla P, Crespo-Facorro B: Grey matter volume differences in non-affective psychosis and the effects of age of onset on grey matter volumes: a voxelwise study. Schizophr Res 2015;164:74-82.
Takahashi T, Wood SJ, Soulsby B, McGorry PD, Tanino R, Suzuki M, Velakoulis D, Pantelis C: Follow-up MRI study of the insular cortex in first-episode psychosis and chronic schizophrenia. Schizophr Res 2009;108:49-56.
Rosa PG, Zanetti MV, Duran FL, Santos LC, Menezes PR, Scazufca M, Murray RM, Busatto GF, Schaufelberger MS: What determines continuing grey matter changes in first-episode schizophrenia and affective psychosis? Psychol Med 2015;45:817-828.
Chen Z, Deng W, Gong Q, Huang C, Jiang L, Li M, He Z, Wang Q, Ma X, Wang Y, Chua SE, McAlonan GM, Sham PC, Collier DA, McGuire P, Li T: Extensive brain structural network abnormality in first-episode treatment-naive patients with schizophrenia: morphometrical and covariation study. Psychol Med 2014;44:2489-2501.
Mané A, Falcon C, Mateos JJ, Fernandez-Egea E, Horga G, Lomeña F, Bargalló N, Prats-Galino A, Bernardo M, Parellada E: Progressive gray matter changes in first episode schizophrenia: a 4-year longitudinal magnetic resonance study using VBM. Schizophr Res 2009;114:136-143.
Ellison-Wright I, Glahn DC, Laird AR, Thelen SM, Bullmore E: The anatomy of first-episode and chronic schizophrenia: an anatomical likelihood estimation meta-analysis. Am J Psychiatry 2008;165:1015-1023.
Chan RC, Di X, McAlonan GM, Gong QY: Brain anatomical abnormalities in high-risk individuals, first-episode, and chronic schizophrenia: an activation likelihood estimation meta-analysis of illness progression. Schizophr Bull 2011;37:177-188.
Moriya J, Kakeda S, Abe O, Goto N, Yoshimura R, Hori H, Ohnari N, Sato T, Aoki S, Ohtomo K, Nakamura J, Korogi Y: Gray and white matter volumetric and diffusion tensor imaging (DTI) analyses in the early stage of first-episode schizophrenia. Schizophr Res 2010;116:196-203.
Hao Y, Liu Z, Jiang T, Gong G, Liu H, Tan L, Kuang F, Xu L, Yi Y, Zhang Z: White matter integrity of the whole brain is disrupted in first-episode schizophrenia. Neuroreport 2006;17:23-26.
Bagary MS, Symms MR, Barker GJ, Mutsatsa SH, Joyce EM, Ron MA: Gray and white matter brain abnormalities in first-episode schizophrenia inferred from magnetization transfer imaging. Arch Gen Psychiatry 2003;60:779-788.
Price G, Cercignani M, Chu EM, Barnes TR, Barker GJ, Joyce EM, Ron MA: Brain pathology in first-episode psychosis: magnetization transfer imaging provides additional information to MRI measurements of volume loss. Neuroimage 2010;49:185-192.
Modinos G, Tseng HH, Falkenberg I, Samson C, McGuire P, Allen P: Neural correlates of aberrant emotional salience predict psychotic symptoms and global functioning in high-risk and first-episode psychosis. Soc Cogn Affect Neurosci 2015;10:1429-1436.
Schmidt A, Palaniyappan L, Smieskova R, Simon A, Riecher-Rössler A, Lang UE, Fusar-Poli P, McGuire P, Borgwardt SJ: Dysfunctional insular connectivity during reward prediction in patients with first-episode psychosis. J Psychiatry Neurosci 2016;41:150234.
Ferri F, Costantini M, Salone A, Ebisch S, De Berardis D, Mazzola V, Arciero G, Ferro FM, Di Giannantonio M, Romani GL, Gallese V: Binding action and emotion in first-episode schizophrenia. Psychopathology 2014;47:394-407.
Sarpal DK, Robinson DG, Lencz T, Argyelan M, Ikuta T, Karlsgodt K, Gallego JA, Kane JM, Szeszko PR, Malhotra AK: Antipsychotic treatment and functional connectivity of the striatum in first-episode schizophrenia. JAMA Psychiatry 2015;72:5-13.
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