Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide
Authors: Liew Sook-Lei , Zavaliangos-Petropulu Artemis , Schweighofer Nicolas , Jahanshad Neda , Lang Catherine E , Lohse Keith R , Banaj Nerisa , Barisano Giuseppe , Baugh Lee A , Bhattacharya Anup K , Bigjahan Bavrina , Borich Michael R , Boyd Lara A , Brodtmann Amy , Buetefisch Cathrin M , Byblow Winston D , Cassidy Jessica M , Charalambous Charalambos C , Ciullo Valentina , Conforto Adriana B , Craddock Richard C , Dula Adrienne N , Egorova Natalia , Feng Wuwei , Fercho Kelene A , Gregory Chris M , Hanlon Colleen A , Hayward Kathryn S , Holguin Jess A , Hordacre Brenton , Hwang Darryl H , Kautz Steven A , Khlif Mohamed Salah , Kim Bokkyu , Kim Hosung , Kuceyeski Amy , Lo Bethany , Liu Jingchun , Lin David , Lotze Martin , MacIntosh Bradley J , Margetis John L , Mohamed Feroze B , Nordvik Jan Egil , Petoe Matthew A , Piras Fabrizio , Raju Sharmila , Ramos-Murguialday Ander , Revill Kate P , Roberts Pamela , Robertson Andrew D , Schambra Heidi M , Seo Na Jin , Shiroishi Mark S , Soekadar Surjo R , Spalletta Gianfranco , Stinear Cathy M , Suri Anisha , Tang Wai Kwong , Thielman Gregory T , Thijs Vincent N , Vecchio Daniela , Ward Nick S , Westlye Lars T , Winstein Carolee J , Wittenberg George F , Wong Kristin A , Yu Chunshui , Wolf Steven L , Cramer Steven C , Thompson Paul M ,   ENIGMA Stroke Recovery Working Group, 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 
Published: October 2021

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 &lt; 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.