Hostname: page-component-7c8c6479df-xxrs7 Total loading time: 0 Render date: 2024-03-28T16:04:53.674Z Has data issue: false hasContentIssue false

Aberrant intrinsic brain activity and cognitive deficit in first-episode treatment-naive patients with schizophrenia

Published online by Cambridge University Press:  10 August 2012

Z. He
Affiliation:
The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China The Fourth People's Hospital of Chengdu, Sichuan, China
W. Deng
Affiliation:
The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
M. Li
Affiliation:
The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
Z. Chen
Affiliation:
The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
L. Jiang
Affiliation:
The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
Q. Wang
Affiliation:
The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
C. Huang
Affiliation:
The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
D. A. Collier
Affiliation:
MRC SGDP Centre, Institute of Psychiatry, King's College London, UK
Q. Gong
Affiliation:
Huaxi MR Research Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
X. Ma
Affiliation:
The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
N. Zhang*
Affiliation:
Center for Comparative Neuroimaging (CCNI), Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, USA
T. Li*
Affiliation:
The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
*
(Email: Nanyin.Zhang@umassmed.edu) [N. Zhang]
*Address for correspondence: Dr T. Li, The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. (Email: xuntao26@hotmail.com) [T. Li]

Abstract

Background

Given the important role of the default mode network (DMN) in cognitive function and the well-known neurocognitive deficit in schizophrenia, it is intriguing to examine systematically the relationship between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia.

Method

First-episode, treatment-naive patients with schizophrenia (FES) (n = 115) and healthy controls (n = 113) underwent resting-state functional magnetic resonance imaging (fMRI) scans and neurocognitive tests. Intrinsic neural activities evaluated by using the fragment amplitude of low-frequency fluctuations (fALFF) and the resting-state functional connectivity assessed by seed-based correlational analysis were compared between patients and controls. Aberrant intrinsic activities and DMN connectivity in patients were then correlated to neurocognitive performance and clinical symptoms.

Results

Compared to controls, patients with FES showed decreased fALFF in the bilateral medial prefrontal cortex (MPFC) and the orbitofrontal cortex (OFC), and increased fALFF in the bilateral putamen. Increased functional connectivity with the DMN was observed in the left insula and bilateral dorsolateral PFC (DLPFC) in patients with FES. In patients, aberrant fALFF in the bilateral OFC were correlated with cognitive processing speed; fALFF in the left OFC and right putamen were correlated with the clinical factors excited/activation and disorganization; and increased DMN functional connectivity in the left insula was correlated with the clinical factors positive, excited/activation, disorganization and neurocognitive deficit in the domain of sustained attention.

Conclusions

These associations between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia may provide important insights into the neural mechanism of the disease.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Annett, M (1970). A classification of hand preference by association analysis. British Journal of Psychology 61, 303321.CrossRefGoogle ScholarPubMed
APA (1994). Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. American Psychiatric Association: Washington, DC.Google Scholar
Bluhm, RL, Miller, J, Lanius, RA, Osuch, EA, Boksman, K, Neufeld, RW, Theberge, J, Schaefer, B, Williamson, P (2007). Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network. Schizophrenia Bulletin 33, 10041012.CrossRefGoogle ScholarPubMed
Bora, E, Fornito, A, Radua, J, Walterfang, M, Seal, M, Wood, SJ, Yücel, M, Velakoulis, D, Pantelis, C (2010). Neuroanatomical abnormalities in schizophrenia: a multimodal voxelwise meta-analysis and meta-regression analysis. Schizophrenia Research 127, 4657.CrossRefGoogle Scholar
Bramham, J, Morris, RG, Hornak, J, Bullock, P, Polkey, CE (2009). Social and emotional functioning following bilateral and unilateral neurosurgical prefrontal cortex lesions. Journal of Neuropsychology 3, 125143.CrossRefGoogle ScholarPubMed
Brandt, GN, Bonelli, RM (2008). Structural neuroimaging of the basal ganglia in schizophrenic patients: a review. Wiener Medizinische Wochenschrift 158, 8490.CrossRefGoogle ScholarPubMed
Broyd, SJ, Demanuele, C, Debener, S, Helps, SK, James, CJ, Sonuga-Barke, EJ (2009). Default-mode brain dysfunction in mental disorders: a systematic review. Neuroscience and Biobehavioral Reviews 33, 279296.CrossRefGoogle ScholarPubMed
Calhoun, VD, Kiehl, KA, Pearlson, GD (2008). Modulation of temporally coherent brain networks estimated using ICA at rest and during cognitive tasks. Human Brain Mapping 29, 828838.CrossRefGoogle ScholarPubMed
Clark, DL, Boutros, NN, Mendez, MF (eds) (2010). The Brain and Behavior: An Introduction to Behavioral Neuroanatomy, pp. 84120. Cambridge University Press: New York.CrossRefGoogle Scholar
Cognition (2004). CANTAB Eclipse Software User Guide. Cambridge Cognition Ltd: Cambridge, UK.Google Scholar
Crespo-Facorro, B, Kim, J, Andreasen, NC, O'Leary, DS, Bockholt, HJ, Magnotta, V (2000). Insular cortex abnormalities in schizophrenia: a structural magnetic resonance imaging study of first-episode patients. Schizophrenia Research 46, 3543.CrossRefGoogle ScholarPubMed
Dickinson, D, Ramsey, ME, Gold, JM (2007). Overlooking the obvious: a meta-analytic comparison of digit symbol coding tasks and other cognitive measures in schizophrenia. Archives of General Psychiatry 64, 532542.CrossRefGoogle ScholarPubMed
First, MB, Spitzer, RL, Williams, JB (1997). Structured Clinical Interview for DSM-IV Axis I Disorders SCID-I. American Psychiatric Publishing Inc.: Washington, DC.Google Scholar
Fox, MD, Raichle, ME (2007). Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nature Reviews Neuroscience 8, 700711.CrossRefGoogle ScholarPubMed
Fox, MD, Snyder, AZ, Vincent, JL, Corbetta, M, Van Essen, DC, Raichle, ME (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences USA 102, 96739678.CrossRefGoogle ScholarPubMed
Fransson, P (2005). Spontaneous low-frequency BOLD signal fluctuations: an fMRI investigation of the resting-state default mode of brain function hypothesis. Human Brain Mapping 26, 1529.CrossRefGoogle ScholarPubMed
Fransson, P, Marrelec, G (2008). The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: evidence from a partial correlation network analysis. NeuroImage 42, 11781184.CrossRefGoogle Scholar
Friston, KJ, Frith, CD (1995). Schizophrenia: a disconnection syndrome. Clinical Neuroscience 3, 8997.Google ScholarPubMed
Garrity, AG, Pearlson, GD, McKiernan, K, Lloyd, D, Kiehl, KA, Calhoun, VD (2007). Aberrant ‘default mode’ functional connectivity in schizophrenia. American Journal of Psychiatry 164, 450457.CrossRefGoogle ScholarPubMed
Goghari, VM, Sponheim, SR, MacDonald, AW 3rd (2010). The functional neuroanatomy of symptom dimensions in schizophrenia: a qualitative and quantitative review of a persistent question. Neuroscience and Biobehavioral Reviews 34, 468486.CrossRefGoogle ScholarPubMed
Hampson, M, Driesen, N, Roth, JK, Gore, JC, Constable, RT (2010). Functional connectivity between task-positive and task-negative brain areas and its relation to working memory performance. Magnetic Resonance Imaging 28, 10511057.CrossRefGoogle ScholarPubMed
Hoptman, MJ, Zuo, XN, Butler, PD, Javitt, DC, D'Angelo, D, Mauro, CJ, Milham, MP (2009). Amplitude of low-frequency oscillations in schizophrenia: a resting state fMRI study. Schizophrenia Research 117, 1320.CrossRefGoogle ScholarPubMed
Howes, OD, Kapur, S (2009). The dopamine hypothesis of schizophrenia: version III – the final common pathway. Schizophrenia Bulletin 35, 549562.CrossRefGoogle ScholarPubMed
Huang, XQ, Lui, S, Deng, W, Chan, RC, Wu, QZ, Jiang, LJ, Zhang, JR, Jia, ZY, Li, XL, Li, F, Chen, L, Li, T, Gong, QY (2010). Localization of cerebral functional deficits in treatment-naive, first-episode schizophrenia using resting-state fMRI. NeuroImage 49, 29012906.CrossRefGoogle ScholarPubMed
Jafri, MJ, Pearlson, GD, Stevens, M, Calhoun, VD (2008). A method for functional network connectivity among spatially independent resting-state components in schizophrenia. NeuroImage 39, 16661681.CrossRefGoogle ScholarPubMed
Kegeles, LS, Abi-Dargham, A, Frankle, WG, Gil, R, Cooper, TB, Slifstein, M, Hwang, DR, Huang, Y, Haber, SN, Laruelle, M (2010). Increased synaptic dopamine function in associative regions of the striatum in schizophrenia. Archives of General Psychiatry 67, 231239.CrossRefGoogle ScholarPubMed
Kelly, AM, Uddin, LQ, Biswal, BB, Castellanos, FX, Milham, MP (2008). Competition between functional brain networks mediates behavioral variability. NeuroImage 39, 527537.CrossRefGoogle ScholarPubMed
Lee, KH, Brown, WH, Egleston, PN, Green, RDJ, Farrow, TFD, Hunter, MD, Parks, RW, Wilkinson, ID, Spence, SA, Woodruff, PWR (2006). A functional magnetic resonance imaging study of social cognition in schizophrenia during an acute episode and after recovery. American Journal of Psychiatry 163, 19261933.CrossRefGoogle ScholarPubMed
Liang, M, Zhou, Y, Jiang, T, Liu, Z, Tian, L, Liu, H, Hao, Y (2006). Widespread functional disconnectivity in schizophrenia with resting-state functional magnetic resonance imaging. NeuroReport 17, 209213.CrossRefGoogle ScholarPubMed
Liu, H, Liu, Z, Liang, M, Hao, Y, Tan, L, Kuang, F, Yi, Y, Xu, L, Jiang, T (2006). Decreased regional homogeneity in schizophrenia: a resting state functional magnetic resonance imaging study. NeuroReport 17, 1922.CrossRefGoogle ScholarPubMed
Liu, Y, Liang, M, Zhou, Y, He, Y, Hao, Y, Song, M, Yu, C, Liu, H, Liu, Z, Jiang, T (2008). Disrupted small-world networks in schizophrenia. Brain 131, 945961.CrossRefGoogle ScholarPubMed
Lui, S, Li, T, Deng, W, Jiang, L, Wu, Q, Tang, H, Yue, Q, Huang, X, Chan, RC, Collier, DA, Meda, SA, Pearlson, G, Mechelli, A, Sweeney, JA, Gong, Q (2010). Short-term effects of antipsychotic treatment on cerebral function in drug-naive first-episode schizophrenia revealed by ‘resting state’ functional magnetic resonance imaging. Archives of General Psychiatry 67, 783792.CrossRefGoogle ScholarPubMed
Mesholam-Gately, RI, Giuliano, AJ, Goff, KP, Faraone, SV, Seidman, LJ (2009). Neurocognition in first-episode schizophrenia: a meta-analytic review. Neuropsychology 23, 315336.CrossRefGoogle ScholarPubMed
Murphy, K, Birn, RM, Handwerker, DA, Jones, TB, Bandettini, PA (2009). The impact of global signal regression on resting state correlations: are anti-correlated networks introduced? NeuroImage 44, 893905.CrossRefGoogle ScholarPubMed
Peruzzo, D, Rambaldelli, G, Bertoldo, A, Bellani, M, Cerini, R, Silvia, M, Pozzi Mucelli, R, Tansella, M, Brambilla, P (2011). The impact of schizophrenia on frontal perfusion parameters: a DSC-MRI study. Journal of Neural Transmission 118, 563570.CrossRefGoogle ScholarPubMed
Pomarol-Clotet, E, Salvador, R, Sarro, S, Gomar, J, Vila, F, Martinez, A, Guerrero, A, Ortiz-Gil, J, Sans-Sansa, B, Capdevila, A, Cebamanos, JM, McKenna, PJ (2008). Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network? Psychological Medicine 38, 11851193.CrossRefGoogle ScholarPubMed
Power, JD, Barnes, KA, Snyder, AZ, Schlaggar, BL, Petersen, SE (2012). Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. NeuroImage 59, 21422154.CrossRefGoogle ScholarPubMed
Raichle, ME, MacLeod, AM, Snyder, AZ, Powers, WJ, Gusnard, DA, Shulman, GL (2001). A default mode of brain function. Proceedings of the National Academy of Sciences USA 98, 676682.CrossRefGoogle ScholarPubMed
Reitan, R (1992). Trail Making Test: Manual for Administration and Scoring. Reitan Neuropsychology Laboratory: Tucson, AZ.Google Scholar
Rotarska-Jagiela, A, van de Ven, V, Oertel-Knochel, V, Uhlhaas, PJ, Vogeley, K, Linden, DE (2010). Resting-state functional network correlates of psychotic symptoms in schizophrenia. Schizophrenia Research 117, 2130.CrossRefGoogle ScholarPubMed
Satterthwaite, TD, Wolf, DH, Loughead, J, Ruparel, K, Elliott, MA, Hakonarson, H, Gur, RC, Gur, RE (2012). Impact of in-scanner head motion on multiple measures of functional connectivity: relevance for studies of neurodevelopment in youth. NeuroImage 60, 623632.CrossRefGoogle ScholarPubMed
Schmitt, GJ, Meisenzahl, EM, Frodl, T, La Fougere, C, Hahn, K, Moller, HJ, Dresel, S (2009). Increase of striatal dopamine transmission in first episode drug-naive schizophrenic patients as demonstrated by [(123)I]IBZM SPECT. Psychiatry Research 173, 183189.CrossRefGoogle Scholar
Snitz, BE, MacDonald, A 3rd, Cohen, JD, Cho, RY, Becker, T, Carter, CS (2005). Lateral and medial hypofrontality in first-episode schizophrenia: functional activity in a medication-naive state and effects of short-term atypical antipsychotic treatment. American Journal of Psychiatry 162, 23222329.CrossRefGoogle Scholar
Sonuga-Barke, EJS, Castellanos, FX (2007). Spontaneous attentional fluctuations in impaired states and pathological conditions: a neurobiological hypothesis. Neuroscience and Biobehavioral Reviews 31, 977986.CrossRefGoogle ScholarPubMed
Townsend, LA, Norman, RMG (2004). Course of cognitive functioning in first-episode schizophrenia spectrum disorders. Expert Review of Neurotherapeutics 4, 6168.CrossRefGoogle ScholarPubMed
Van den Oord, EJCG, Rujescu, D, Robles, JR, Giegling, I, Birrell, C, Bukszár, J, Murrelle, L, Möller, HJ, Middleton, L, Muglia, P (2006). Factor structure and external validity of the PANSS revisited. Schizophrenia Research 82, 213223.CrossRefGoogle ScholarPubMed
Van Dijk, KRA, Sabuncu, MR, Buckner, RL (2012). The influence of head motion on intrinsic functional connectivity MRI. NeuroImage 59, 431438.CrossRefGoogle ScholarPubMed
Venkatasubramanian, G (2007). Schizophrenia is a disorder of aberrant neurodevelopment: a synthesis of evidence from clinical and structural, functional and neurochemical brain imaging studies. Indian Journal of Psychiatry 49, 244249.CrossRefGoogle ScholarPubMed
Wang, L, Metzak, PD, Woodward, TS (2010 a). Aberrant connectivity during self–other source monitoring in schizophrenia. Schizophrenia Research 125, 136142.CrossRefGoogle ScholarPubMed
Wang, Q, Vassos, E, Deng, W, Ma, X, Hu, X, Murray, RM, Collier, DA, Li, T (2010 b). Factor structures of the neurocognitive assessments and familial analysis in first-episode schizophrenia patients, their relatives and controls. Australian and New Zealand Journal of Psychiatry 44, 109119.CrossRefGoogle ScholarPubMed
Wechsler, D (1987). Instruction Manual for the Wechsler Memory Scale – Revised Psychological Corporation: New York.Google Scholar
Wechsler, D (1981). WAIS-R Manual: Wechsler Adult Intelligence Scale – Revised. Psychological Corporation: New YorkGoogle Scholar
Whitfield-Gabrieli, S, Thermenos, HW, Milanovic, S, Tsuang, MT, Faraone, SV, McCarley, RW, Shenton, ME, Green, AI, Nieto-Castanon, A, LaViolette, P (2009). Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia. Proceedings of the National Academy of Sciences USA 106, 12791284.CrossRefGoogle ScholarPubMed
Williamson, P (2007). Are anticorrelated networks in the brain relevant to schizophrenia? Schizophrenia Bulletin 33, 9941004.CrossRefGoogle ScholarPubMed
Witthaus, H, Kaufmann, C, Bohner, G, Ögüdal, S, Gudlowski, Y, Gallinat, J, Ruhrmann, S, Brüe, M, Heinz, A, Klingebiel, R, Juckel, G (2009). Gray matter abnormalities in subjects at ultra-high risk for schizophrenia and first-episode schizophrenic patients compared to healthy controls. Psychiatry Research: Neuroimaging 173, 163169.CrossRefGoogle ScholarPubMed
Wylie, KP, Tregellas, JR (2010). The role of the insula in schizophrenia. Schizophrenia Research 123, 93104.CrossRefGoogle ScholarPubMed
Zhou, Y, Liang, M, Tian, L, Wang, K, Hao, Y, Liu, H, Liu, Z, Jiang, T (2007). Functional disintegration in paranoid schizophrenia using resting-state fMRI. Schizophrenia Research 97, 194205.CrossRefGoogle ScholarPubMed
Zou, QH, Zhu, CZ, Yang, YH, Zuo, XN, Long, XY, Cao, QJ, Wang, YF, Zang, YF (2008). An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF. Journal of Neuroscience Methods 172, 137141.CrossRefGoogle ScholarPubMed