Distinct manifestation of cognitive deficits associate with different resting-state network disruptions in non-demented patients with Parkinson’s disease

  • Kazuya Kawabata
  • Hirohisa Watanabe
  • Kazuhiro Hara
  • Epifanio Bagarinao
  • Noritaka Yoneyama
  • Aya Ogura
  • Kazunori Imai
  • Michihito Masuda
  • Takamasa Yokoi
  • Reiko Ohdake
  • Yasuhiro Tanaka
  • Takashi Tsuboi
  • Tomohiko Nakamura
  • Masaaki Hirayama
  • Mizuki Ito
  • Naoki Atsuta
  • Satoshi Maesawa
  • Shinji Naganawa
  • Masahisa Katsuno
  • Gen Sobue
Original Communication

Abstract

Cognitive deficits in Parkinson’s disease (PD) are heterogeneous entities, but a relationship between the heterogeneity of cognitive deficits and resting-state network (RSN) changes remains elusive. In this study, we examined five sub-domain scores according to Addenbrooke’s Cognitive Examination-Revised (ACE-R) for the cognitive evaluation and classification of 72 non-demented patients with PD. Twenty-eight patients were classified as PD with normal cognition (PD-NC). The remaining 44 were subdivided into the following 2 groups using a hierarchical cluster analysis: 20 with a predominant decrease in memory (PD with amnestic cognitive deficits: PD-A) and 24 with good memory who exhibited a decrease in other sub-domains (PD with non-amnestic cognitive deficits: PD-NA). We used an independent component analysis of RS-fMRI data to investigate the inter-group differences of RSN. Compared to the controls, the PD-A showed lower FC within the ventral default mode network (vDMN) and the visuospatial network. On the other hand, the PD-NA showed lower FC within the visual networks and the cerebellum–brainstem network. Significant differences in the FC within the vDMN and cerebellum–brainstem network were observed between the PD-A and PD-NA, which provided a good discrimination between PD-A and PD-NA using a support vector machine. Distinct patterns of cognitive deficits correspond to different RSN changes.

Keywords

Parkinson’s disease Cognitive deficits Resting-state fMRI Independent component analysis Resting-state network Functional connectivity 

Notes

Acknowledgements

This study was partially supported by a Grant-in-Aid from the Research Committee of Central Nervous System Degenerative Diseases by the Ministry of Health, Labour, and Welfare, Integrated Research on Neuropsychiatric Disorders project carried out Strategic Research Program for Brain Sciences (SRPBS), a Grant-in-Aid for Scientific Research on Innovative Areas (Brain Protein Aging and Dementia Control 26117002) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, as well as Integrated Research on neuropsychiatric disorders carried out under the SRPBS, Scientific Research on Innovative Areas (Comprehensive Brain Science Network), and Integrated Research on Depression, Dementia and Development Disorders by SRPBS from Japan Agency for Medical Research and development.

Compliance with ethical standards

Conflicts of interest

All authors declared no conflict of interest.

Ethical standards

This study conformed to the Ethical Guidelines for Medical and Health Research Involving Human Subjects endorsed by the Japanese government and was approved by the Ethics Committee of Nagoya University Graduate School of Medicine.

Supplementary material

415_2018_8755_MOESM1_ESM.docx (1.2 mb)
Supplementary material 1 (DOCX 1201 kb)

References

  1. 1.
    Aarsland D, Perry R, Brown A, Larsen JP, Ballard C (2005) Neuropathology of dementia in Parkinson’s disease: a prospective, community-based study. Ann Neurol 58:773–776CrossRefPubMedGoogle Scholar
  2. 2.
    Abe Y, Kachi T, Kato T, Arahata Y, Yamada T, Washimi Y, Iwai K, Ito K, Yanagisawa N, Sobue G (2003) Occipital hypoperfusion in Parkinson’s disease without dementia: correlation to impaired cortical visual processing. J Neurol Neurosurg Psychiatry 74:419–422CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Agosta F, Canu E, Stefanova E, Sarro L, Tomic A, Spica V, Comi G, Kostic VS, Filippi M (2014) Mild cognitive impairment in Parkinson’s disease is associated with a distributed pattern of brain white matter damage. Hum Brain Mapp 35:1921–1929CrossRefPubMedGoogle Scholar
  4. 4.
    Agosta F, Kostic VS, Davidovic K, Kresojevic N, Sarro L, Svetel M, Stankovic I, Comi G, Klein C, Filippi M (2013) White matter abnormalities in Parkinson’s disease patients with glucocerebrosidase gene mutations. Mov Disord 28:772–778CrossRefPubMedGoogle Scholar
  5. 5.
    Ashburner J (2007) A fast diffeomorphic image registration algorithm. Neuroimage 38:95–113CrossRefPubMedGoogle Scholar
  6. 6.
    Baciu M, Boudiaf N, Cousin E, Perrone-Bertolotti M, Pichat C, Fournet N, Chainay H, Lamalle L, Krainik A (2016) Functional MRI evidence for the decline of word retrieval and generation during normal aging. Age (Dordr) 38:3CrossRefGoogle Scholar
  7. 7.
    Baggio HC, Sala-Llonch R, Segura B, Marti MJ, Valldeoriola F, Compta Y, Tolosa E, Junque C (2014) Functional brain networks and cognitive deficits in Parkinson’s disease. Hum Brain Mapp 35:4620–4634CrossRefPubMedGoogle Scholar
  8. 8.
    Baggio HC, Segura B, Sala-Llonch R, Marti MJ, Valldeoriola F, Compta Y, Tolosa E, Junque C (2015) Cognitive impairment and resting-state network connectivity in Parkinson’s disease. Hum Brain Mapp 36:199–212CrossRefPubMedGoogle Scholar
  9. 9.
    Barkhof F, Haller S, Rombouts SA (2014) Resting-state functional MR imaging: a new window to the brain. Radiology 272:29–49CrossRefPubMedGoogle Scholar
  10. 10.
    Beckmann CF, DeLuca M, Devlin JT, Smith SM (2005) Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc Lond B Biol Sci 360:1001–1013CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Berankova D, Janousova E, Mrackova M, Eliasova I, Kostalova M, Skutilova S, Rektorova I (2015) Addenbrooke’s cognitive examination and individual domain cut-off scores for discriminating between different cognitive subtypes of parkinson’s disease. Parkinsons Dis 2015:579417PubMedPubMedCentralGoogle Scholar
  12. 12.
    Birn RM, Kenworthy L, Case L, Caravella R, Jones TB, Bandettini PA, Martin A (2010) Neural systems supporting lexical search guided by letter and semantic category cues: a self-paced overt response fMRI study of verbal fluency. Neuroimage 49:1099–1107CrossRefPubMedGoogle Scholar
  13. 13.
    Bohnen NI, Koeppe RA, Minoshima S, Giordani B, Albin RL, Frey KA, Kuhl DE (2011) Cerebral glucose metabolic features of Parkinson disease and incident dementia: longitudinal study. J Nucl Med 52:848–855CrossRefPubMedGoogle Scholar
  14. 14.
    Bohnen NI, Minoshima S, Giordani B, Frey KA, Kuhl DE (1999) Motor correlates of occipital glucose hypometabolism in Parkinson’s disease without dementia. Neurology 52:541–546CrossRefPubMedGoogle Scholar
  15. 15.
    Caillava-Santos F, Margis R, de Mello Rieder CR (2015) Wearing-off in Parkinson’s disease: neuropsychological differences between on and off periods. Neuropsychiatr Dis Treat 11:1175–1180CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Chang C-C (2011) LIBSVM: a library for support vector machines. ACM Trans Intell Syst Technol 2:3–27CrossRefGoogle Scholar
  17. 17.
    Cholerton BA, Zabetian CP, Wan JY, Montine TJ, Quinn JF, Mata IF, Chung KA, Peterson A, Espay AJ, Revilla FJ, Devoto J, Watson GS, Hu SC, Leverenz JB, Edwards KL (2014) Evaluation of mild cognitive impairment subtypes in Parkinson’s disease. Mov Disord 29:756–764CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Cortes C, Vapnik V (1995) Support-vector networks. Mach Learn 20:273–297Google Scholar
  19. 19.
    Cortese A, Amano K, Koizumi A, Lau H, Kawato M (2017) Decoded fMRI neurofeedback can induce bidirectional confidence changes within single participants. Neuroimage 149:323–337CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Delgado-Alvarado M, Gago B, Navalpotro-Gomez I, Jimenez-Urbieta H, Rodriguez-Oroz MC (2016) Biomarkers for dementia and mild cognitive impairment in Parkinson’s disease. Mov Disord 31:861–881CrossRefPubMedGoogle Scholar
  21. 21.
    Dos Santos Kawata KH, Hashimoto R, Nishio Y, Hayashi A, Ogawa N, Kanno S, Hiraoka K, Yokoi K, Iizuka O, Mori E (2012) A validation study of the Japanese version of the Addenbrooke’s cognitive examination-revised. Dement Geriatr Cogn Dis Extra 2:29–37CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Dubois B, Burn D, Goetz C, Aarsland D, Brown RG, Broe GA, Dickson D, Duyckaerts C, Cummings J, Gauthier S, Korczyn A, Lees A, Levy R, Litvan I, Mizuno Y, McKeith IG, Olanow CW, Poewe W, Sampaio C, Tolosa E, Emre M (2007) Diagnostic procedures for Parkinson’s disease dementia: recommendations from the movement disorder society task force. Mov Disord 22:2314–2324CrossRefPubMedGoogle Scholar
  23. 23.
    Eberling JL, Richardson BC, Reed BR, Wolfe N, Jagust WJ (1994) Cortical glucose metabolism in Parkinson’s disease without dementia. Neurobiol Aging 15:329–335CrossRefPubMedGoogle Scholar
  24. 24.
    Eickhoff SB, Stephan KE, Mohlberg H, Grefkes C, Fink GR, Amunts K, Zilles K (2005) A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data. Neuroimage 25:1325–1335CrossRefPubMedGoogle Scholar
  25. 25.
    Eidelberg D (2009) Metabolic brain networks in neurodegenerative disorders: a functional imaging approach. Trends Neurosci 32:548–557CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Esposito F, Tessitore A, Giordano A, De Micco R, Paccone A, Conforti R, Pignataro G, Annunziato L, Tedeschi G (2013) Rhythm-specific modulation of the sensorimotor network in drug-naive patients with Parkinson’s disease by levodopa. Brain 136:710–725CrossRefPubMedGoogle Scholar
  27. 27.
    Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA (1987) MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol 149:351–356CrossRefPubMedGoogle Scholar
  28. 28.
    Filippini N, MacIntosh BJ, Hough MG, Goodwin GM, Frisoni GB, Smith SM, Matthews PM, Beckmann CF, Mackay CE (2009) Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proc Natl Acad Sci USA 106:7209–7214CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Fox MD, Greicius M (2010) Clinical applications of resting state functional connectivity. Front Syst Neurosci 4:19PubMedPubMedCentralGoogle Scholar
  30. 30.
    Gottlich M, Munte TF, Heldmann M, Kasten M, Hagenah J, Kramer UM (2013) Altered resting state brain networks in Parkinson’s disease. PLoS ONE 8:e77336CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Harrington DL, Shen Q, Castillo GN, Filoteo JV, Litvan I, Takahashi C, French C (2017) Aberrant intrinsic activity and connectivity in cognitively normal Parkinson’s disease. Front Aging Neurosci 9:197CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Hendershott TR, Zhu D, Llanes S, Poston KL (2017) Domain-specific accuracy of the montreal cognitive assessment subsections in Parkinson’s disease. Parkinsonism Relat Disord 38:31–34CrossRefPubMedGoogle Scholar
  33. 33.
    Hughes AJ, Ben-Shlomo Y, Daniel SE, Lees AJ (1992) What features improve the accuracy of clinical diagnosis in Parkinson’s disease: a clinicopathologic study. Neurology 42:1142–1146CrossRefPubMedGoogle Scholar
  34. 34.
    Irwin DJ, Grossman M, Weintraub D, Hurtig HI, Duda JE, Xie SX, Lee EB, Van Deerlin VM, Lopez OL, Kofler JK, Nelson PT, Jicha GA, Woltjer R, Quinn JF, Kaye J, Leverenz JB, Tsuang D, Longfellow K, Yearout D, Kukull W, Keene CD, Montine TJ, Zabetian CP, Trojanowski JQ (2017) Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: a retrospective analysis. Lancet Neurol 16:55–65CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Jenkinson M, Beckmann CF, Behrens TE, Woolrich MW, Smith SM (2012) Fsl. Neuroimage 62:782–790CrossRefPubMedGoogle Scholar
  36. 36.
    Kalaitzakis ME, Christian LM, Moran LB, Graeber MB, Pearce RK, Gentleman SM (2009) Dementia and visual hallucinations associated with limbic pathology in Parkinson’s disease. Parkinsonism Relat Disord 15:196–204CrossRefPubMedGoogle Scholar
  37. 37.
    Kansal K, Yang Z, Fishman AM, Sair HI, Ying SH, Jedynak BM, Prince JL, Onyike CU (2017) Structural cerebellar correlates of cognitive and motor dysfunctions in cerebellar degeneration. Brain 140:707–720PubMedGoogle Scholar
  38. 38.
    Kashihara K, Kondo T, Mizuno Y, Kikuchi S, Kuno S, Hasegawa K, Hattori N, Mochizuki H, Mori H, Murata M, Nomoto M, Takahashi R, Takeda A, Tsuboi Y, Ugawa Y, Yamanmoto M, Yokochi F, Yoshii F, Stebbins GT, Tilley BC, Luo S, Wang L, LaPelle NR, Goetz CG, Group M-UJVS (2014) Official Japanese Version of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale: validation against the original English version. Mov Disord Clin Pract 1:200–212CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Kehagia AA, Barker RA, Robbins TW (2010) Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson’s disease. Lancet Neurol 9:1200–1213CrossRefPubMedGoogle Scholar
  40. 40.
    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. J Neural Transm (Vienna) 119:443–454CrossRefGoogle Scholar
  41. 41.
    Laird AR, Fox PM, Eickhoff SB, Turner JA, Ray KL, McKay DR, Glahn DC, Beckmann CF, Smith SM, Fox PT (2011) Behavioral interpretations of intrinsic connectivity networks. J Cogn Neurosci 23:4022–4037CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Lin CH, Wu RM (2015) Biomarkers of cognitive decline in Parkinson’s disease. Parkinsonism Relat Disord 21:431–443CrossRefPubMedGoogle Scholar
  43. 43.
    Litvan I, Goldman JG, Troster AI, Schmand BA, Weintraub D, Petersen RC, Mollenhauer B, Adler CH, Marder K, Williams-Gray CH, Aarsland D, Kulisevsky J, Rodriguez-Oroz MC, Burn DJ, Barker RA, Emre M (2012) Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: Movement Disorder Society Task Force guidelines. Mov Disord 27:349–356CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    McColgan P, Evans JR, Breen DP, Mason SL, Barker RA, Williams-Gray CH (2012) Addenbrooke’s Cognitive Examination-Revised for mild cognitive impairment in Parkinson’s disease. Mov Disord 27:1173–1177CrossRefPubMedGoogle Scholar
  45. 45.
    Mioshi E, Dawson K, Mitchell J, Arnold R, Hodges JR (2006) The Addenbrooke’s Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry 21:1078–1085CrossRefPubMedGoogle Scholar
  46. 46.
    Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699CrossRefPubMedGoogle Scholar
  47. 47.
    Ng B, Varoquaux G, Poline JB, Thirion B, Greicius MD, Poston KL (2017) Distinct alterations in Parkinson’s medication-state and disease-state connectivity. Neuroimage Clin 16:575–585CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Nichols TE, Holmes AP (2002) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 15:1–25CrossRefPubMedGoogle Scholar
  49. 49.
    Olde Dubbelink KT, Schoonheim MM, Deijen JB, Twisk JW, Barkhof F, Berendse HW (2014) Functional connectivity and cognitive decline over 3 years in Parkinson disease. Neurology 83:2046–2053CrossRefPubMedGoogle Scholar
  50. 50.
    Pedersen KF, Larsen JP, Tysnes OB, Alves G (2017) Natural course of mild cognitive impairment in Parkinson disease: a 5-year population-based study. Neurology 88:767–774CrossRefPubMedGoogle Scholar
  51. 51.
    Peraza LR, Nesbitt D, Lawson RA, Duncan GW, Yarnall AJ, Khoo TK, Kaiser M, Firbank MJ, O’Brien JT, Barker RA, Brooks DJ, Burn DJ, Taylor JP (2017) Intra- and inter-network functional alterations in Parkinson’s disease with mild cognitive impairment. Hum Brain Mapp 38:1702–1715CrossRefPubMedGoogle Scholar
  52. 52.
    Petersen RC, Morris JC (2005) Mild cognitive impairment as a clinical entity and treatment target. Arch Neurol 62:1160–1163 (discussion 1167) CrossRefPubMedGoogle Scholar
  53. 53.
    Petrou M, Dwamena BA, Foerster BR, MacEachern MP, Bohnen NI, Muller ML, Albin RL, Frey KA (2015) Amyloid deposition in Parkinson’s disease and cognitive impairment: a systematic review. Mov Disord 30:928–935CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    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 59:2142–2154CrossRefPubMedGoogle Scholar
  55. 55.
    Reginold W, Duff-Canning S, Meaney C, Armstrong MJ, Fox S, Rothberg B, Zadikoff C, Kennedy N, Gill D, Eslinger P, Marshall F, Mapstone M, Chou KL, Persad C, Litvan I, Mast B, Tang-Wai D, Lang AE, Marras C (2013) Impact of mild cognitive impairment on health-related quality of life in Parkinson’s disease. Dement Geriatr Cogn Disord 36:67–75CrossRefPubMedGoogle Scholar
  56. 56.
    Rittman T, Ghosh BC, McColgan P, Breen DP, Evans J, Williams-Gray CH, Barker RA, Rowe JB (2013) The Addenbrooke’s Cognitive Examination for the differential diagnosis and longitudinal assessment of patients with parkinsonian disorders. J Neurol Neurosurg Psychiatry 84:544–551CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Robbins TW, Cools R (2014) Cognitive deficits in Parkinson’s disease: a cognitive neuroscience perspective. Mov Disord 29:597–607CrossRefPubMedGoogle Scholar
  58. 58.
    Scharnowski F, Veit R, Zopf R, Studer P, Bock S, Diedrichsen J, Goebel R, Mathiak K, Birbaumer N, Weiskopf N (2015) Manipulating motor performance and memory through real-time fMRI neurofeedback. Biol Psychol 108:85–97CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Shirer WR, Ryali S, Rykhlevskaia E, Menon V, Greicius MD (2012) Decoding subject-driven cognitive states with whole-brain connectivity patterns. Cereb Cortex 22:158–165CrossRefPubMedGoogle Scholar
  60. 60.
    Smith SM, Fox PT, Miller KL, Glahn DC, Fox PM, Mackay CE, Filippini N, Watkins KE, Toro R, Laird AR, Beckmann CF (2009) Correspondence of the brain’s functional architecture during activation and rest. Proc Natl Acad Sci USA 106:13040–13045CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Stoodley CJ, Valera EM, Schmahmann JD (2012) Functional topography of the cerebellum for motor and cognitive tasks: an fMRI study. Neuroimage 59:1560–1570CrossRefPubMedGoogle Scholar
  62. 62.
    Szewczyk-Krolikowski K, Menke RA, Rolinski M, Duff E, Salimi-Khorshidi G, Filippini N, Zamboni G, Hu MT, Mackay CE (2014) Functional connectivity in the basal ganglia network differentiates PD patients from controls. Neurology 83:208–214CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Tahmasian M, Bettray LM, van Eimeren T, Drzezga A, Timmermann L, Eickhoff CR, Eickhoff SB, Eggers C (2015) A systematic review on the applications of resting-state fMRI in Parkinson’s disease: does dopamine replacement therapy play a role? Cortex 73:80–105CrossRefPubMedGoogle Scholar
  64. 64.
    Tessitore A, Esposito F, Vitale C, Santangelo G, Amboni M, Russo A, Corbo D, Cirillo G, Barone P, Tedeschi G (2012) Default-mode network connectivity in cognitively unimpaired patients with Parkinson disease. Neurology 79:2226–2232CrossRefPubMedGoogle Scholar
  65. 65.
    Utevsky AV, Smith DV, Huettel SA (2014) Precuneus is a functional core of the default-mode network. J Neurosci 34:932–940CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Wei Q, Chen X, Zheng Z, Huang R, Guo X, Cao B, Bak TH, Shang H (2015) Screening for cognitive impairment in a Chinese ALS population. Amyotroph Lateral Scler Frontotemporal Degener 16:40–45CrossRefPubMedGoogle Scholar
  67. 67.
    Weil RS, Schrag AE, Warren JD, Crutch SJ, Lees AJ, Morris HR (2016) Visual dysfunction in Parkinson’s disease. Brain 139:2827–2843CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Backman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de Leon M, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van Duijn C, Visser P, Petersen RC (2004) Mild cognitive impairment–beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256:240–246CrossRefPubMedGoogle Scholar
  69. 69.
    Wu T, Hallett M (2013) The cerebellum in Parkinson’s disease. Brain 136:696–709CrossRefPubMedGoogle Scholar
  70. 70.
    Yahata N, Morimoto J, Hashimoto R, Lisi G, Shibata K, Kawakubo Y, Kuwabara H, Kuroda M, Yamada T, Megumi F, Imamizu H, Nanez JE Sr, Takahashi H, Okamoto Y, Kasai K, Kato N, Sasaki Y, Watanabe T, Kawato M (2016) A small number of abnormal brain connections predicts adult autism spectrum disorder. Nat Commun 7:11254CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Kazuya Kawabata
    • 1
    • 2
  • Hirohisa Watanabe
    • 1
    • 2
  • Kazuhiro Hara
    • 1
  • Epifanio Bagarinao
    • 2
  • Noritaka Yoneyama
    • 3
  • Aya Ogura
    • 1
  • Kazunori Imai
    • 1
  • Michihito Masuda
    • 1
  • Takamasa Yokoi
    • 1
  • Reiko Ohdake
    • 2
  • Yasuhiro Tanaka
    • 1
  • Takashi Tsuboi
    • 1
  • Tomohiko Nakamura
    • 1
  • Masaaki Hirayama
    • 4
  • Mizuki Ito
    • 1
  • Naoki Atsuta
    • 1
  • Satoshi Maesawa
    • 5
  • Shinji Naganawa
    • 6
  • Masahisa Katsuno
    • 1
  • Gen Sobue
    • 2
    • 7
  1. 1.Department of NeurologyNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Brain and Mind Research CenterNagoya UniversityNagoyaJapan
  3. 3.Department of NeurologyHanda City HospitalHandaJapan
  4. 4.Department of Pathophysiological Laboratory SciencesNagoya University Graduate School of MedicineNagoyaJapan
  5. 5.Department of NeurosurgeryNagoya University Graduate School of MedicineNagoyaJapan
  6. 6.Department of RadiologyNagoya University Graduate School of MedicineNagoyaJapan
  7. 7.Research Division of Dementia and Neurodegenerative DiseaseNagoya University Graduate School of MedicineNagoyaJapan

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