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Salience and Default Mode Network Coupling Predicts Cognition in Aging and Parkinson’s Disease

Published online by Cambridge University Press:  18 February 2016

Deepti Putcha*
Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts
Robert S. Ross
Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts Department of Psychology, University of New Hampshire, Durham, New Hampshire
Alice Cronin-Golomb
Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts
Amy C. Janes
Brain Imaging Center, McLean Hospital, Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts
Chantal E. Stern
Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts
Correspondence and reprint requests to: Deepti Putcha, 2 Cummington Mall, Center for Memory and Brain, Boston University, Boston, MA 02215. E-mail:


Objectives: Cognitive impairment is common in Parkinson’s disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants. Methods: We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains. Results: PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson’s disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling. Conclusions: Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson’s disease. (JINS, 2016, 22, 205–215)

Research Articles
Copyright © The International Neuropsychological Society 2016 

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Aarsland, D., Andersen, K., Larsen, J.P., Lolk, A., & Kragh-Sorensen, P. (2003). Prevalence and characteristics of dementia in Parkinson disease: An 8-year prospective study. Archives of Neurology, 60(3), 387392.Google Scholar
Barone, P., Aarsland, D., Burn, D., Emre, M., Kulisevsky, J., & Weintraub, D. (2011). Cognitive impairment in nondemented Parkinson’s disease. Movement Disorders, 26(14), 24832495. doi:10.1002/mds.23919 Google Scholar
Beckmann, C.F., Mackay, C.E., Filippini, N., & Smith, S.M. (2009). Group comparison of resting-state FMRI data using multi-subject ICA and dual regression. Paper presented at the OHBM.Google Scholar
Bonnelle, V., Ham, T.E., Leech, R., Kinnunen, K.M., Mehta, M.A., Greenwood, R.J., && Sharp, D.J. (2012). Salience network integrity predicts default mode network function after traumatic brain injury. Proceedings of the National Academy of Sciences of the United States of America, 109(12), 46904695. doi:10.1073/pnas.1113455109 Google Scholar
Bosboom, J.L., Stoffers, D., & Wolters, E. (2004). Cognitive dysfunction and dementia in Parkinson’s disease. Journal of Neural Transmission, 111(10-11), 13031315. doi:10.1007/s00702-004-0168-1 Google Scholar
Bressler, S.L., & Menon, V. (2010). Large-scale brain networks in cognition: Emerging methods and principles. Trends in Cognitive Sciences, 14(6), 277290. doi:10.1016/j.tics.2010.04.004 Google Scholar
Bronnick, K., Alves, G., Aarsland, D., Tysnes, O.B., & Larsen, J.P. (2011). Verbal memory in drug-naive, newly diagnosed Parkinson’s disease. The retrieval deficit hypothesis revisited. Neuropsychology, 25(1), 114124. doi:10.1037/a0020857 Google Scholar
Buckner, R.L., Andrews-Hanna, J.R., & Schacter, D.L. (2008). The brain’s default network: Anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences, 1124, 138.Google Scholar
Buddenberg, L.A., & Davis, C. (2000). Test-retest reliability of the Purdue Pegboard Test. The American Journal of Occupational Therapy, 54(5), 555558.Google Scholar
Chikama, M., McFarland, N.R., Amaral, D.G., & Haber, S.N. (1997). Insular cortical projections to functional regions of the striatum correlate with cortical cytoarchitectonic organization in the primate. The Journal of Neuroscience, 17(24), 96869705.Google Scholar
Chiong, W., Wilson, S.M., D’Esposito, M., Kayser, A.S., Grossman, S.N., Poorzand, P., & Rankin, K.P. (2013). The salience network causally influences default mode network activity during moral reasoning. Brain, 136(Pt 6), 19291941. doi:10.1093/brain/awt066 Google Scholar
Christopher, L., Duff-Canning, S., Koshimori, Y., Segura, B., Boileau, I., Chen, R., & Strafella, A.P. (2015). Salience network and parahippocampal dopamine dysfunction in memory-impaired Parkinson disease. Annals of Neurology, 77(2), 269280. doi:10.1002/ana.24323 Google Scholar
Christopher, L., Koshimori, Y., Lang, A.E., Criaud, M., & Strafella, A.P. (2014). Uncovering the role of the insula in non-motor symptoms of Parkinson’s disease. Brain, 137, 21432154. doi:awu084 [pii]Google Scholar
Christopher, L., Marras, C., Duff-Canning, S., Koshimori, Y., Chen, R., Boileau, I., & Strafella, A.P. (2014). Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson’s disease with mild cognitive impairment. Brain, 137(Pt 2), 565575. doi:awt337 [pii]Google Scholar
Cole, D.M., Beckmann, C.F., Long, C.J., Matthews, P.M., Durcan, M.J., & Beaver, J.D. (2010). Nicotine replacement in abstinent smokers improves cognitive withdrawal symptoms with modulation of resting brain network dynamics. Neuroimage, 52(2), 590599. doi:10.1016/j.neuroimage.2010.04.251 Google Scholar
Dikmen, S.S., Heaton, R.K., Grant, I., & Temkin, N.R. (1999). Test-retest reliability and practice effects of expanded Halstead-Reitan Neuropsychological Test Battery. Journal of the International Neuropsychological Society, 5(4), 346356.Google Scholar
Dirnberger, G., & Jahanshahi, M. (2013). Executive dysfunction in Parkinson’s disease: A review. Journal of Neuropsychology, 7(2), 193224. doi:10.1111/jnp.12028 Google Scholar
Disbrow, E.A., Carmichael, O., He, J., Lanni, K.E., Dressler, E.M., Zhang, L., & Sigvardt, K.A. (2014). Resting state functional connectivity is associated with cognitive dysfunction in non-demented people with Parkinson’s disease. Journal of Parkinsons Disease, 4, 453465. doi:1J0371M16R3R8714 [pii]Google Scholar
Dosenbach, N.U., Visscher, K.M., Palmer, E.D., Miezin, F.M., Wenger, K.K., Kang, H.C., & Petersen, S.E. (2006). A core system for the implementation of task sets. Neuron, 50(5), 799812. doi:S0896-6273(06)00349-7 [pii]Google Scholar
Doyen, A.L., & Carlier, M. (2002). Measuring handedness: A validation study of Bishop’s reaching card test. Laterality, 7(2), 115130. doi:10.1080/13576500143000140 Google Scholar
Duan, X., Liao, W., Liang, D., Qiu, L., Gao, Q., Liu, C., & Chen, H. (2012). Large-scale brain networks in board game experts: Insights from a domain-related task and task-free resting state. PLoS One, 7(3), e32532. doi:10.1371/journal.pone.0032532 Google Scholar
Filippini, N., MacIntosh, B.J., Hough, M.G., Goodwin, G.M., Frisoni, G.B., Smith, S.M., & Mackay, C.E. (2009). Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proceedings of the National Academy of Sciences of the United States of America, 106(17), 72097214. doi:0811879106 [pii].Google Scholar
Foltynie, T., Brayne, C.E., Robbins, T.W., & Barker, R.A. (2004). The cognitive ability of an incident cohort of Parkinson’s patients in the UK. The CamPaIGN study. Brain, 127(Pt 3), 550560. doi:10.1093/brain/awh067 Google Scholar
Fox, M.D., Snyder, A.Z., Vincent, J.L., Corbetta, M., Van Essen, D.C., & Raichle, M.E. (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences of the United States of America, 102(27), 96739678.Google Scholar
Fox, M.D., Snyder, A.Z., Vincent, J.L., & Raichle, M.E. (2007). Intrinsic fluctuations within cortical systems account for intertrial variability in human behavior. Neuron, 56(1), 171184. doi:S0896-6273(07)00666-6 [pii]Google Scholar
Fox, P.T., Laird, A.R., Fox, S.P., Fox, P.M., Uecker, A.M., Crank, M., & Lancaster, J.L. (2005). BrainMap taxonomy of experimental design: Description and evaluation. Human Brain Mapping, 25(1), 185198. doi:10.1002/hbm.20141 Google Scholar
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(3), 11781184.Google Scholar
Fudge, J.L., Breitbart, M.A., Danish, M., & Pannoni, V. (2005). Insular and gustatory inputs to the caudal ventral striatum in primates. Journal of Comparitive Neurology, 490(2), 101118. doi:10.1002/cne.20660 Google Scholar
Greicius, M.D., Krasnow, B., Reiss, A.L., & Menon, V. (2003). Functional connectivity in the resting brain: A network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences of the United States of America, 100(1), 253258. doi:10.1073/pnas.0135058100 Google Scholar
Huang, C., Mattis, P., Tang, C., Perrine, K., Carbon, M., & Eidelberg, D. (2007). Metabolic brain networks associated with cognitive function in Parkinson’s disease. Neuroimage, 34(2), 714723. doi:10.1016/j.neuroimage.2006.09.003 Google Scholar
Janes, A.C., Farmer, S., Frederick, B., Nickerson, L.D., & Lukas, S.E. (2014). An increase in tobacco craving is associated with enhanced medial prefrontal cortex network coupling. PLoS One, 9(2), e88228. doi:10.1371/journal.pone.0088228 Google Scholar
Janvin, C., Aarsland, D., Larsen, J.P., & Hugdahl, K. (2003). Neuropsychological profile of patients with Parkinson’s disease without dementia. Dementia and Geriatric Cognitive Disorders, 15(3), 126131. doi:68483 Google Scholar
Janvin, C., Larsen, J.P., Aarsland, D., & Hugdahl, K. (2006). Subtypes of mild cognitive impairment in Parkinson’s disease: Progression to dementia. Movement Disorders, 21(9), 13431349. doi:10.1002/mds.20974 Google Scholar
Jilka, S.R., Scott, G., Ham, T., Pickering, A., Bonnelle, V., Braga, R.M., & Sharp, D.J. (2014). Damage to the salience network and interactions with the default mode network. Journal of Neuroscience, 34(33), 1079810807. doi:10.1523/JNEUROSCI.0518-14.2014 Google Scholar
Kelly, A.M., Uddin, L.Q., Biswal, B.B., Castellanos, F.X., & Milham, M.P. (2008). Competition between functional brain networks mediates behavioral variability. Neuroimage, 39(1), 527537. doi:10.1016/j.neuroimage.2007.08.008 Google Scholar
Kish, S.J., Shannak, K., & Hornykiewicz, O. (1988). Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease. Pathophysiologic and clinical implications. New England Journal of Medicine, 318(14), 876880. doi:10.1056/NEJM198804073181402 Google Scholar
Klepac, N., Trkulja, V., Relja, M., & Babic, T. (2008). Is quality of life in non-demented Parkinson’s disease patients related to cognitive performance? A clinic-based cross-sectional study. European Journal of Neurology, 15(2), 128133. doi:10.1111/j.1468-1331.2007.02011.x Google Scholar
Kortte, K.B., Horner, M.D., & Windham, W.K. (2002). The trail making test, part B: Cognitive flexibility or ability to maintain set? Applied Neuropsychology, 9(2), 106109. doi:10.1207/S15324826AN0902_5 Google Scholar
Krajcovicova, L., Mikl, M., Marecek, R., & Rektorova, I. (2012). The default mode network integrity in patients with Parkinson’s disease is levodopa equivalent dose-dependent. Journal of Neural Transmission, 119(4), 443454. doi:10.1007/s00702-011-0723-5 Google Scholar
Kudlicka, A., Clare, L., & Hindle, J.V. (2011). Executive functions in Parkinson’s disease: Systematic review and meta-analysis. Movement Disorders, 26(13), 23052315. doi:10.1002/mds.23868 Google Scholar
Laird, A.R., Fox, P.M., Eickhoff, S.B., Turner, J.A., Ray, K.L., McKay, D.R., & Fox, P.T. (2011). Behavioral interpretations of intrinsic connectivity networks. Journal of Cognitive Neuroscience, 23(12), 40224037. doi:10.1162/jocn_a_00077 Google Scholar
Laird, A.R., Lancaster, J.L., & Fox, P.T. (2005). BrainMap: The social evolution of a human brain mapping database. Neuroinformatics, 3(1), 6578. doi:NI:3:1:065 [pii]Google Scholar
Lakens, D. (2013). Calculating and reporting effect sizes to facilitate cumulative science: A practical primer for t-tests and ANOVAs. Frontiers in Psychology, 4, 863. doi:10.3389/fpsyg.2013.00863 Google Scholar
Leech, R., & Sharp, D.J. (2014). The role of the posterior cingulate cortex in cognition and disease. Brain, 137(Pt 1), 1232. doi:10.1093/brain/awt162 Google Scholar
Lewis, S.J., Cools, R., Robbins, T.W., Dove, A., Barker, R.A., & Owen, A.M. (2003). Using executive heterogeneity to explore the nature of working memory deficits in Parkinson’s disease. Neuropsychologia, 41(6), 645654.Google Scholar
Lewis, S.J., Dove, A., Robbins, T.W., Barker, R.A., & Owen, A.M. (2003). Cognitive impairments in early Parkinson’s disease are accompanied by reductions in activity in frontostriatal neural circuitry. The Journal of Neuroscience, 23(15), 63516356. doi:23/15/6351 [pii]Google Scholar
Lewis, S.J., Slabosz, A., Robbins, T.W., Barker, R.A., & Owen, A.M. (2005). Dopaminergic basis for deficits in working memory but not attentional set-shifting in Parkinson’s disease. Neuropsychologia, 43(6), 823832. doi:S0028-3932(04)00266-0 [pii]Google Scholar
Mamikonyan, E., Moberg, P.J., Siderowf, A., Duda, J.E., Have, T.T., Hurtig, H.I., & Weintraub, D. (2009). Mild cognitive impairment is common in Parkinson’s disease patients with normal Mini-Mental State Examination (MMSE) scores. Parkinsonism & Related Disorders, 15(3), 226231. doi:10.1016/j.parkreldis.2008.05.006 Google Scholar
Martinu, K., Degroot, C., Madjar, C., Strafella, A.P., & Monchi, O. (2012). Levodopa influences striatal activity but does not affect cortical hyper-activity in Parkinson’s disease. European Journal of Neuroscience, 35, 572583. doi:10.1111/j.1460-9568.2011 Google Scholar
Menon, V. (2011). Large-scale brain networks and psychopathology: A unifying triple network model. Trends in Cognitive Sciences, 15(10), 483506. doi:S1364-6613(11)00171-9 [pii]Google Scholar
Menon, V., & Uddin, L.Q. (2010). Saliency, switching, attention and control: A network model of insula function. Brain Structure & Function, 214(5-6), 655667. doi:10.1007/s00429-010-0262-0 Google Scholar
Middleton, F.A., & Strick, P.L. (2000). Basal ganglia and cerebellar loops: Motor and cognitive circuits. Brain Research. Brain Research Reviews, 31(2-3), 236250. doi:S0165017399000405 [pii]Google Scholar
Miller, I.N., Neargarder, S., Risi, M.M., & Cronin-Golomb, A. (2013). Frontal and posterior subtypes of neuropsychological deficit in Parkinson’s disease. Behavioral Neuroscience, 127(2), 175183. doi:10.1037/a0031357 Google Scholar
Mitrushina, M., Satz, P., Chervinsky, A., & D’Elia, L. (1991). Performance of four age groups of normal elderly on the Rey Auditory-Verbal Learning Test. Journal of Clinical Psychology, 47(3), 351357.Google Scholar
Monchi, O., Petrides, M., Mejia-Constain, B., & Strafella, A.P. (2006). Cortical activity in Parkinson’s disease during executive processing depends on striatal involvement. Brain, 130(Pt 1), 233244. doi:awl326 [pii]Google Scholar
Moustafa, A.A., Krishna, R., Eissa, A.M., & Hewedi, D.H. (2013). Factors underlying probabilistic and deterministic stimulus-response learning performance in medicated and unmedicated patients with Parkinson’s disease. Neuropsychology, 27(4), 498510. doi:2013-25138-010 [pii]Google Scholar
Narayanan, N.S., Rodnitzky, R.L., & Uc, E.Y. (2013). Prefrontal dopamine signaling and cognitive symptoms of Parkinson’s disease. Reviews in the Neurosciences, 24(3), 267278. doi:10.1515/revneuro-2013-0004 Google Scholar
Poletti, M., & Bonuccelli, U. (2013). Acute and chronic cognitive effects of levodopa and dopamine agonists on patients with Parkinson’s disease: A review. Therapeutic Advances in Psychopharmacology, 3(2), 101113. doi:10.1177/2045125312470130 Google Scholar
Postuma, R.B., & Dagher, A. (2006). Basal ganglia functional connectivity based on a meta-analysis of 126 positron emission tomography and functional magnetic resonance imaging publications. Cerebral Cortex, 16(10), 15081521. doi:bhj088 [pii]Google Scholar
Putcha, D., Ross, R.S., Cronin-Golomb, A., Janes, A.C., & Stern, C.E. (2015). Altered intrinsic functional coupling between core neurocognitive networks in Parkinson’s disease. Neuroimage. Clinical, 7, 449455. doi:10.1016/j.nicl.2015.01.012 Google Scholar
Raichle, M.E., MacLeod, A.M., Snyder, A.Z., Powers, W.J., Gusnard, D.A., & Shulman, G.L. (2001). A default mode of brain function. Proceedings of the National Academy of Sciences of the United States of America, 98(2), 676682.Google Scholar
Ravina, B., Marek, K., Eberly, S., Oakes, D., Kurlan, R., Ascherio, A., & Shoulson, I. (2012). Dopamine transporter imaging is associated with long-term outcomes in Parkinson’s disease. Movement Disorders, 27(11), 13921397. doi:10.1002/mds.25157 Google Scholar
Rey, A. (1964). L’examen clinique en psychologie. Paris: Presses Universitaires de France.Google Scholar
Schendan, H.E., Tinaz, S., Maher, S.M., & Stern, C.E. (2013). Frontostriatal and mediotemporal lobe contributions to implicit higher-order spatial sequence learning declines in aging and Parkinson’s disease. Behavioral Neuroscience, 127(2), 204221. doi:2013-11369-003 [pii]Google Scholar
Seeley, W.W., Menon, V., Schatzberg, A.F., Keller, J., Glover, G.H., Kenna, H., & Greicius, M.D. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. The Journal of Neuroscience, 27(9), 23492356. doi:27/9/2349 [pii]Google Scholar
Spreng, R.N., Mar, R.A., & Kim, A.S. (2009). The common neural basis of autobiographical memory, prospection, navigation, theory of mind, and the default mode: A quantitative meta-analysis. Journal of Cognitive Neuroscience, 21(3), 489510. doi:10.1162/jocn.2008.21029 Google Scholar
Sridharan, D., Levitin, D.J., & Menon, V. (2008). A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proceedings of the National Academy of Sciences of the United States of America, 105(34), 1256912574. doi:0800005105 [pii]Google Scholar
Strauss, E., Sherman, E., & Spreen, O. (2006). A compendium of neuropsychological tests: Administration, norms, and commentaryed (3rd ed.). Cambridge: Oxford University Press.Google Scholar
Tessitore, A., Esposito, F., Vitale, C., Santangelo, G., Amboni, M., Russo, A., & Tedeschi, G. (2012). Default-mode network connectivity in cognitively unimpaired patients with Parkinson disease. Neurology, 79(23), 22262232. doi:WNL.0b013e31827689d6 [pii]Google Scholar
Tiffin, J., & Asher, E.J. (1948). The Purdue pegboard; Norms and studies of reliability and validity. Journal of Applied Psychology, 32(3), 234247.Google Scholar
Tinaz, S., Lauro, P., Hallett, M., & Horovitz, S.G. (2015). Deficits in task-set maintenance and execution networks in Parkinson’s disease. Brain Structure & Function. doi:10.1007/s00429-014-0981-8 Google Scholar
Tinaz, S., Schendan, H.E., & Stern, C.E. (2008). Fronto-striatal deficit in Parkinson’s disease during semantic event sequencing. Neurobiology of Aging, 29(3), 397407. doi:S0197-4580(06)00400-3 [pii]Google Scholar
Tombaugh, T.N. (2004). Trail Making Test A and B: Normative data stratified by age and education. Archives of Clinical Neuropsychology, 19(2), 203214. doi:10.1016/S0887-6177(03)00039-8 Google Scholar
Uc, E.Y., McDermott, M.P., Marder, K.S., Anderson, S.W., Litvan, I., Como, P.G., … Parkinson Study Group DATATOP Investigators. (2009). Incidence of and risk factors for cognitive impairment in an early Parkinson disease clinical trial cohort. Neurology, 73(18), 14691477. doi:10.1212/WNL.0b013e3181bf992f Google Scholar
Uc, E.Y., Rizzo, M., Anderson, S.W., Qian, S., Rodnitzky, R.L., & Dawson, J.D. (2005). Visual dysfunction in Parkinson disease without dementia. Neurology, 65(12), 19071913. doi:01.wnl.0000191565.11065.11 [pii]Google Scholar
van Eimeren, T., Monchi, O., Ballanger, B., & Strafella, A.P. (2009). Dysfunction of the default mode network in Parkinson disease: A functional magnetic resonance imaging study. Archives of Neurology, 66(7), 877883. doi:66/7/877 [pii]Google Scholar
Weissman, D.H., Roberts, K.C., Visscher, K.M., & Woldorff, M.G. (2006). The neural bases of momentary lapses in attention. Nature Neuroscience, 9(7), 971978. doi:10.1038/nn1727 Google Scholar
Williams-Gray, C.H., Evans, J.R., Goris, A., Foltynie, T., Ban, M., Robbins, T.W., & Barker, R.A. (2009). The distinct cognitive syndromes of Parkinson’s disease: 5 year follow-up of the CamPaIGN cohort. Brain, 132(Pt 11), 29582969. doi:awp245 [pii]Google Scholar