Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide

Author:

Liew Sook-Lei12ORCID,Zavaliangos-Petropulu Artemis34,Schweighofer Nicolas5,Jahanshad Neda4,Lang Catherine E678,Lohse Keith R9,Banaj Nerisa10,Barisano Giuseppe311ORCID,Baugh Lee A12131415,Bhattacharya Anup K16ORCID,Bigjahan Bavrina17,Borich Michael R18,Boyd Lara A19ORCID,Brodtmann Amy2021,Buetefisch Cathrin M182223,Byblow Winston D24,Cassidy Jessica M25ORCID,Charalambous Charalambos C2627ORCID,Ciullo Valentina10,Conforto Adriana B2829,Craddock Richard C30,Dula Adrienne N30,Egorova Natalia2031ORCID,Feng Wuwei32,Fercho Kelene A3334,Gregory Chris M32,Hanlon Colleen A3536,Hayward Kathryn S203738ORCID,Holguin Jess A1,Hordacre Brenton39ORCID,Hwang Darryl H1740ORCID,Kautz Steven A3241,Khlif Mohamed Salah20,Kim Bokkyu42,Kim Hosung2,Kuceyeski Amy43,Lo Bethany1,Liu Jingchun44,Lin David45ORCID,Lotze Martin46ORCID,MacIntosh Bradley J4748,Margetis John L1,Mohamed Feroze B49,Nordvik Jan Egil50ORCID,Petoe Matthew A5152,Piras Fabrizio10,Raju Sharmila53ORCID,Ramos-Murguialday Ander5455,Revill Kate P56,Roberts Pamela15758,Robertson Andrew D5960ORCID,Schambra Heidi M53,Seo Na Jin324161ORCID,Shiroishi Mark S417,Soekadar Surjo R62,Spalletta Gianfranco1063,Stinear Cathy M64ORCID,Suri Anisha65,Tang Wai Kwong66,Thielman Gregory T67,Thijs Vincent N2068,Vecchio Daniela10,Ward Nick S69,Westlye Lars T7071ORCID,Winstein Carolee J572,Wittenberg George F7374,Wong Kristin A75,Yu Chunshui4476,Wolf Steven L7778798081,Cramer Steven C5872,Thompson Paul M4,Banaj Nerisa,Barisano Giuseppe,Baugh Lee,Gallaguet Adrià Bermudo,Bhattacharya Anup,Bigjahan Bavrina,Borich Michael,Boyd Lara,Brodtmann Amy,Brown Truman,Buetefisch Cathrin,Byblow Winston,Cassidy Jessica,Charalambous Charalambos,Ciullo Valentina,Cloutier Alison,Cole James,Conforto Adriana,Craddock Richard,Cramer Steven,Aguayo Rosalia Dacosta,DiCarlo Julie,Dimyan Michael,Domin Martin,Donnellly Miranda,Dula Adrienne,Edwardson Matthew,Egorova Natalia,Ermer Elsa,Etherton Mark,Feng Wuwei,Fercho Kelene,Ferris Jennifer,Geranmayeh Fatemeh,Gregory Chris,Hadidchi Shahram,Hanlon Colleen,Hayes Leticia,Hayward Kathryn,Holguin Jess,Hordacre Brenton,Hwang Darryl,Jahanshad Neda,Jamison Keith,Juliano Julia,Kautz Steven,Khlif Mohamed Salah,Kim Bokkyu,Kim Hosung,Kuceyeski Amy,Lang Catherine,Lee Jenny,Liew Sook-Lei,Lin David,Liu Jingchun,Lo Bethany,Lohse Keith,Lotze Martin,MacIntosh Bradley,Margetis John,Margulies Daniel,Mataro Maria,McGregor Keith,Mohamed Feroze,Nordvik Jan,Olafson Emily,Perera-LLuna Alexandre,Petoe Matthew,Phillips Aaron,Piras Fabrizio,Raju Sharmila,Ramos-Murguialday Ander,Revill Kate,Roberts Pamela,Robertson Andrew,Rondina Jane,Rost Natalia,Sanossian Nerses,Schambra Heidi,Schranz Christian,Schweighofer Nicolas,Seo Na Jin,Sepehrband Farshid,Shiroishi Mark,Simon Julia,Soekadar Surjo,Spalletta Gianfranco,Srivastava Shraddha,Stewart Jill,Stinear Cathy,Suri Anisha,Taga Myriam,Tang Wai Kwong,Thielman Gregory,Thijs Vincent,Thomopoulos Sophia,Thompson Paul,Vecchio Daniela,Warach Steven,Ward Nick,Werden Emilio,Westlye Lars,Wiest Roland,Winstein Carolee,Wittenberg George,Wolf Steven,Wong Kristin,Yu Chunshui,Zavaliangos-Petropulu Artemis,

Affiliation:

1. Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA, USA

2. Keck School of Medicine, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA

3. Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA

4. Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA

5. Biokinesiology and Physical Therapy, Ostrow School of Medicine, University of Southern California, Los Angeles, CA, USA

6. Departments of Physical Therapy, Washington University School of Medicine, St. Louis, MO, USA

7. Department of Occupational Therapy, Washington University School of Medicine, St. Louis, MO, USA

8. Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA

9. Department of Health and Kinesiology, University of Utah, Salt Lake City, UT, USA

10. Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy

11. Laboratory of Neuro Imaging, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

12. Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA

13. Sioux Falls VA Health Care System, Sioux Falls, SD, USA

14. Center for Brain and Behavior Research, Vermillion, SD, USA

15. Sanford Research, Sioux Falls, SD, USA

16. Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA

17. Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

18. Department of Rehabilitation Medicine, Emory University, Atlanta, GA, USA

19. Department of Physical Therapy & the Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

20. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, VIC, Australia

21. Eastern Cognitive Disorders Clinic, Monash University, Melbourne, VIC, Australia

22. Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA

23. Department of Radiology, Emory University, Atlanta, GA, USA

24. Department of Exercise Sciences and Centre for Brain Research, University of Auckland, Auckland, New Zealand

25. Allied Health Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

26. Department of Basic and Clinical Sciences, University of Nicosia Medical School, Nicosia, Cyprus

27. Center for Neuroscience and Integrative Brain Research (CENIBRE), University of Nicosia Medical School, Nicosia, Cyprus

28. Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil

29. Hospital Israelita Albert Einstein, São Paulo, SP, Brazil

30. Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX, USA

31. Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, VIC, Australia

32. Department of Health Sciences & Research, Medical University of South Carolina, Charleston, SC, USA

33. Civil Aerospace Medical Institute, US Federal Aviation Administration, Oklahoma City, OK, USA

34. Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA

35. Cancer Biology, Wake Forest School of Medicine, Winston Salem, NC, USA

36. College of Health Professions, Medical University of South Carolina, Charleston, SC, USA

37. Department of Physiotherapy, University of Melbourne, Heidelberg, VIC, Australia

38. NHMRC CRE in Stroke Rehabilitation and Brain Recovery, University of Melbourne, Heidelberg, VIC, Australia

39. Innovation, IMPlementation and Clinical Translation (IIMPACT) in Health, Allied Health and Human Performance, University of South Australia, Adelaide, SA, Australia

40. Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA

41. Ralph H. Johnson VA Medical Center, Charleston, SC, USA

42. Department of Physical Therapy Education, College of Health Professions, SUNY Upstate Medical University, Syracuse, NY, USA

43. Department of Radiology, Weill Cornell Medicine, New York, NY, USA

44. Department of Radiology, Tianjin Medical University General Hospital, Tianjin, China

45. Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

46. Department of Diagnostic Radiology, University Medicine Greifswald, Greifswald, Germany

47. Hurvitz Brain Sciences, Sunnybrook Research Institute, Toronto, ON, Canada

48. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

49. Jefferson Integrated Magnetic Resonance Imaging Center, Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA

50. CatoSenteret Rehabilitation Center, Son, Norway

51. Bionics Institute, Melbourne, VIC, Australia

52. Department of Medicine and Centre for Brain Research, University of Auckland, Auckland, New Zealand

53. Department of Neurology, New York University Langone, New York, NY, USA

54. TECNALIA, Basque Research and Technology Alliance (BRTA), Health Division, San Sebastian Donostia, Spain

55. Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany

56. Facility for Education and Research in Neuroscience, Emory University, Atlanta, GA, USA

57. Department of Physical Medicine and Rehabilitation, Cedars-Sinai, Los Angeles, CA, USA

58. California Rehabilitation Institute, Los Angeles, CA, USA

59. Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada

60. Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada

61. Department of Rehabilitation Sciences, Medical University of South Carolina, Charleston, SC, USA

62. Clinical Neurotechnology Laboratory, Department of Psychiatry and Psychotherapy, Charité - University Medicine Berlin, Berlin, Germany

63. Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA

64. Department of Medicine, University of Auckland, Auckland, New Zealand

65. Department of Electrical and Computer Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA

66. Department of Psychiatry, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, China

67. Department of Physical Therapy and Neuroscience, University of the Sciences, Philadelphia, PA, USA

68. Department of Neurology, Austin Health, Heidelberg, VIC, Australia

69. UCL Queen Square Institute of Neurology, London, UK

70. Department of Psychology, University of Oslo, Oslo, Norway

71. NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway

72. Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA

73. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA

74. Neurology, Department of Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA

75. Department of Physical Medicine & Rehabilitation, Dell Medical School, University of Texas at Austin, Austin, TX, USA

76. Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, China

77. Division of Physical Therapy Education, Department of Rehabilitation Medicine, Emory University School of Medicine, Atlanta, GA, USA

78. Division of Physical Therapy Education, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

79. Division of Physical Therapy Education, Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA

80. Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA

81. Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Health Care System, Decatur, GA, USA

Abstract

Abstract Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P < 0.004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behaviour was associated with a smaller ipsilesional thalamic volume in both early (n = 179; d = 0.68) and subacute (n = 274, d = 0.46) stroke. In chronic stroke (n = 404), worse sensorimotor behaviour was associated with smaller ipsilesional putamen (d = 0.52) and nucleus accumbens (d = 0.39) volumes, and a larger ipsilesional lateral ventricle (d = −0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n = 256) was associated with smaller ipsilesional putamen (d = 0.72) and larger lateral ventricle (d = −0.41) volumes, while several measures of activity limitations (n = 116) showed no significant relationships. In the full cohort across all time (n = 828), sensorimotor behaviour was associated with the volumes of the ipsilesional nucleus accumbens (d = 0.23), putamen (d = 0.33), thalamus (d = 0.33) and lateral ventricle (d = −0.23). We demonstrate significant relationships between post-stroke sensorimotor behaviour and reduced volumes of deep grey matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings provide additional insight into how different cortico-thalamo-striatal circuits support post-stroke sensorimotor outcomes.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

General Earth and Planetary Sciences,General Environmental Science

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