Hostname: page-component-7c8c6479df-7qhmt Total loading time: 0 Render date: 2024-03-29T12:59:39.075Z Has data issue: false hasContentIssue false

Aberrant functional connectivity of dorsolateral prefrontal and cingulate networks in patients with major depression during working memory processing

Published online by Cambridge University Press:  10 October 2008

N. Vasic*
Affiliation:
Department of Psychiatry and Psychotherapy III, University of Ulm, Germany
H. Walter
Affiliation:
Department of Psychiatry, Division of Medical Psychology, University of Bonn, Germany
F. Sambataro
Affiliation:
Clinical Brain Disorders Branch, Genes Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
R. C. Wolf
Affiliation:
Department of Psychiatry and Psychotherapy III, University of Ulm, Germany
*
*Address for correspondence: N. Vasic, M.D., University of Ulm, Department of Psychiatry and Psychotherapy, Leimgrubenweg 12–14, 89075 Ulm, Germany. (Email: nenad.vasic@uni-ulm.de)

Abstract

Background

In patients with major depressive disorder (MDD), functional neuroimaging studies have reported an increased activation of the dorsolateral prefrontal cortex (DLPFC) during executive performance and working memory (WM) processing, and also an increased activation of the anterior cingulate cortex (ACC) during baseline conditions. However, the functional coupling of these cortical networks during WM processing is less clear.

Method

In this study, we used a verbal WM paradigm, event-related functional magnetic resonance imaging (fMRI) and multivariate statistical techniques to explore patterns of functional coupling of temporally dissociable dorsolateral prefrontal and cingulate networks. By means of independent component analyses (ICAs), two components of interest were identified that showed either a positive or a negative temporal correlation with the delay period of the cognitive activation task in both healthy controls and MDD patients.

Results

In a prefronto-parietal network, a decreased functional connectivity pattern was identified in depressed patients comprising inferior parietal, superior prefrontal and frontopolar regions. Within this cortical network, MDD patients additionally revealed a pattern of increased functional connectivity in the left DLPFC and the cerebellum compared to healthy controls. In a second, temporally anti-correlated network, healthy controls exhibited higher connectivity in the ACC, the ventrolateral and the superior prefrontal cortex compared to MDD patients.

Conclusions

These results complement and expand previous functional neuroimaging findings by demonstrating a dysconnectivity of dissociable prefrontal and cingulate regions in MDD patients. A disturbance of these dynamic networks is characterized by a simultaneously increased connectivity of the DLPFC during task-induced activation and increased connectivity of the ACC during task-induced deactivation.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2008

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

Austin, MP, Mitchell, P, Wilhelm, K, Parker, G, Hickie, I, Brodaty, H, Chan, J, Eyers, K, Milic, M, Hadzi-Pavlovic, D (1999). Cognitive function in depression: a distinct pattern of frontal impairment in melancholia? Psychological Medicine 29, 7385.CrossRefGoogle ScholarPubMed
Baddeley, A (2003). Working memory: looking back and looking forward. Nature Reviews. Neuroscience 4, 829839.Google Scholar
Bartels, A, Zeki, S (2004). The chronoarchitecture of the human brain – natural viewing conditions reveal a time-based anatomy of the brain. Neuroimage 22, 419433.CrossRefGoogle ScholarPubMed
Bunge, SA, Klingberg, T, Jacobsen, RB, Gabrieli, JD (2000). A resource model of the neural basis of executive working memory. Proceedings of the National Academy of Sciences USA 97, 35733578.CrossRefGoogle ScholarPubMed
Calhoun, VD, Adali, T, Pearlson, GD, Pekar, JJ (2001). A method for making group inferences from functional MRI data using independent component analysis. Human Brain Mapping 14, 140151.CrossRefGoogle ScholarPubMed
Calhoun, VD, Adali, T, Pekar, JJ (2004). A method for comparing group fMRI data using independent component analysis: application to visual, motor and visuomotor tasks. Magnetic Resonance Imaging 22, 11811191.CrossRefGoogle ScholarPubMed
Celone, KA, Calhoun, VD, Dickerson, BC, Atri, A, Chua, EF, Miller, SL, DePeau, K, Rentz, DM, Selkoe, DJ, Blacker, D, Albert, MS, Sperling, RA (2006). Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis. Journal of Neuroscience 26, 1022210231.CrossRefGoogle ScholarPubMed
Correa, N, Adali, T, Yi-Ou, L, Calhoun, VD (2005). Comparison of blind source separation algorithms for fMRI using a new Matlab toolbox: GIFT. Proceedings of the IEEE International Conference on Acoustics, Speech and Signal Processing 5, 401404.Google Scholar
Desmond, JE, Chen, SH, DeRosa, E, Pryor, MR, Pfefferbaum, A, Sullivan, EV (2003). Increased frontocerebellar activation in alcoholics during verbal working memory: an fMRI study. Neuroimage 19, 15101520.CrossRefGoogle ScholarPubMed
D'Esposito, M, Postle, BR, Rypma, B (2000). Prefrontal cortical contributions to working memory: evidence from event-related fMRI studies. Experimental Brain Research 133, 311.CrossRefGoogle ScholarPubMed
Drevets, WC (2000). Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression. Progress in Brain Research 126, 413431.CrossRefGoogle ScholarPubMed
Duvernoy, HM (1999). The Human Brain. Springer: Wien/New York.CrossRefGoogle Scholar
Forman, SD, Cohen, JD, Fitzgerald, M, Eddy, WF, Mintun, MA, Noll, DC (1995). Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold. Magnetic Resonance in Medicine 33, 636647.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 (2006). How default is the default mode of brain function? Further evidence from intrinsic BOLD signal fluctuations. Neuropsychologia 44, 28362845.CrossRefGoogle 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
Genovese, CR, Lazar, NA, Nichols, T (2002). Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage 15, 870878.CrossRefGoogle ScholarPubMed
Gottwald, B, Wilde, B, Mihajlovic, Z, Mehdorn, HM (2004). Evidence for distinct cognitive deficits after focal cerebellar lesions. Journal of Neurology, Neurosurgery and Psychiatry 75, 15241531.CrossRefGoogle ScholarPubMed
Greicius, MD, Flores, BH, Menon, V, Glover, GH, Solvason, HB, Kenna, H, Reiss, AL, Schatzberg, AF (2007). Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biological Psychiatry 62, 429437.CrossRefGoogle ScholarPubMed
Greicius, MD, Menon, V (2004). Default-mode activity during a passive sensory task: uncoupled from deactivation but impacting activation. Journal of Cognitive Neuroscience 16, 14841492.CrossRefGoogle ScholarPubMed
Harvey, PO, Fossati, P, Pochon, JB, Levy, R, Lebastard, G, Lehericy, S, Allilaire, JF, Dubois, B (2005). Cognitive control and brain resources in major depression: an fMRI study using the n-back task. Neuroimage 26, 860869.CrossRefGoogle ScholarPubMed
Harvey, PO, Le Bastard, G, Pochon, JB, Levy, R, Allilaire, JF, Dubois, B, Fossati, P (2004). Executive functions and updating of the contents of working memory in unipolar depression. Journal of Psychiatric Research 38, 567576.CrossRefGoogle ScholarPubMed
Haynes, LE, Barber, D, Mitchell, IJ (2004). Chronic antidepressant medication attenuates dexamethasone-induced neuronal death and sublethal neuronal damage in the hippocampus and striatum. Brain Research 1026, 157167.CrossRefGoogle ScholarPubMed
Hugdahl, K, Rund, BR, Lund, A, Asbjornsen, A, Egeland, J, Ersland, L, Landro, NI, Roness, A, Stordal, KI, Sundet, K, Thomsen, T (2004). Brain activation measured with fMRI during a mental arithmetic task in schizophrenia and major depression. American Journal of Psychiatry 161, 286293.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
Kane, MJ, Engle, RW (2002). The role of prefrontal cortex in working-memory capacity, executive attention, and general fluid intelligence: an individual-differences perspective. Psychonomic Bulletin and Review 9, 637671.CrossRefGoogle ScholarPubMed
Kosten, TA, Galloway, MP, Duman, RS, Russell, DS, D'Sa, C (2008). Repeated unpredictable stress and antidepressants differentially regulate expression of the Bcl-2 family of apoptotic genes in rat cortical, hippocampal, and limbic brain structures. Neuropsychopharmacology 33, 15451548.CrossRefGoogle ScholarPubMed
Li, YO, Adali, T, Calhoun, VD (2007). Estimating the number of independent components for functional magnetic resonance imaging data. Human Brain Mapping 28, 12511266.CrossRefGoogle ScholarPubMed
Liotti, M, Mayberg, HS, McGinnis, S, Brannan, SL, Jerabek, P (2002). Unmasking disease-specific cerebral blood flow abnormalities: mood challenge in patients with remitted unipolar depression. American Journal of Psychiatry 159, 18301840.CrossRefGoogle ScholarPubMed
Matsuo, K, Glahn, DC, Peluso, MA, Hatch, JP, Monkul, ES, Najt, P, Sanches, M, Zamarripa, F, Li, J, Lancaster, JL, Fox, PT, Gao, JH, Soares, JC (2007). Prefrontal hyperactivation during working memory task in untreated individuals with major depressive disorder. Molecular Psychiatry 12, 158166.CrossRefGoogle ScholarPubMed
Mayberg, HS (2003). Positron emission tomography imaging in depression: a neural systems perspective. Neuroimaging Clinics of North America 13, 805815.CrossRefGoogle ScholarPubMed
Mazoyer, B, Zago, L, Mellet, E, Bricogne, S, Etard, O, Houde, O, Crivello, F, Joliot, M, Petit, L, Tzourio-Mazoyer, N (2001). Cortical networks for working memory and executive functions sustain the conscious resting state in man. Brain Research Bulletin 54, 287298.CrossRefGoogle ScholarPubMed
Okada, G, Okamoto, Y, Morinobu, S, Yamawaki, S, Yokota, N (2003). Attenuated left prefrontal activation during a verbal fluency task in patients with depression. Neuropsychobiology 47, 2126.CrossRefGoogle ScholarPubMed
Oldfield, RC (1971). The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97113.CrossRefGoogle ScholarPubMed
Owen, AM, McMillan, KM, Laird, AR, Bullmore, E (2005). N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies. Human Brain Mapping 25, 4659.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
Rose, EJ, Simonotto, E, Ebmeier, KP (2006 a). Limbic over-activity in depression during preserved performance on the n-back task. Neuroimage 29, 203215.CrossRefGoogle ScholarPubMed
Rose, EJ, Simonotto, E, Spencer, EP, Ebmeier, KP (2006 b). The effects of escitalopram on working memory and brain activity in healthy adults during performance of the n-back task. Psychopharmacology (Berlin) 185, 339347.CrossRefGoogle ScholarPubMed
Schmahmann, JD, Sherman, JC (1998). The cerebellar cognitive affective syndrome. Brain 121, 561579.CrossRefGoogle ScholarPubMed
Sternberg, S (1966). High-speed scanning in human memory. Science 153, 652654.CrossRefGoogle ScholarPubMed
Storey, JD, Tibshirani, R (2003). Statistical significance for genomewide studies. Proceedings of the National Academy of Sciences USA 100, 94409445.CrossRefGoogle ScholarPubMed
Talairach, J, Tournoux, P (1988). Co-Planar Stereotaxic Atlas of the Human Brain. Thieme: New York.Google Scholar
Tavano, A, Grasso, R, Gagliardi, C, Triulzi, F, Bresolin, N, Fabbro, F, Borgatti, R (2007). Disorders of cognitive and affective development in cerebellar malformations. Brain 130, 26462660.CrossRefGoogle ScholarPubMed
Vasic, N, Wolf, RC, Walter, H (2007). Executive functions in patients with depression – the role of prefrontal activation. Nervenarzt 78, 628640.CrossRefGoogle ScholarPubMed
Walsh, ND, Williams, SC, Brammer, MJ, Bullmore, ET, Kim, J, Suckling, J, Mitterschiffthaler, MT, Cleare, AJ, Pich, EM, Mehta, MA, Fu, CH (2007). A longitudinal functional magnetic resonance imaging study of verbal working memory in depression after antidepressant therapy. Biological Psychiatry 62, 12361243.CrossRefGoogle ScholarPubMed
Walter, H, Vasic, N, Hose, A, Spitzer, M, Wolf, RC (2007 a). Working memory dysfunction in schizophrenia compared to healthy controls and patients with depression: evidence from event-related fMRI. Neuroimage 35, 15511561.CrossRefGoogle ScholarPubMed
Walter, H, Wolf, RC, Spitzer, M, Vasic, N (2007 b). Increased left prefrontal activation in patients with unipolar depression: an event-related, parametric, performance-controlled fMRI study. Journal of Affective Disorders 101, 175185.CrossRefGoogle ScholarPubMed
Wolf, RC, Walter, H (2005). Evaluation of a novel event-related parametric fMRI paradigm investigating prefrontal function. Psychiatry Research 140, 7383.CrossRefGoogle ScholarPubMed
Zakzanis, KK, Leach, L, Kaplan, E (1998). On the nature and pattern of neurocognitive function in major depressive disorder. Neuropsychiatry, Neuropsychology and Behavioral Neurology 11, 111119.Google ScholarPubMed
Zhang, JX, Leung, HC, Johnson, MK (2003). Frontal activations associated with accessing and evaluating information in working memory: an fMRI study. Neuroimage 20, 15311539.CrossRefGoogle ScholarPubMed
Ziemus, B, Baumann, O, Luerding, R, Schlosser, R, Schuierer, G, Bogdahn, U, Greenlee, MW (2007). Impaired working-memory after cerebellar infarcts paralleled by changes in BOLD signal of a cortico-cerebellar circuit. Neuropsychologia 45, 20162024.CrossRefGoogle ScholarPubMed