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    Upper-Limb Motor Intervention Elements That Drive Improvement in Biomarkers and Clinical Measures Post-Stroke: A Systematic Review in a Systems Paradigm
    Wingfield, M ; Fini, NA ; Brodtmann, A ; Williams, G ; Churilov, L ; Hayward, KS (SAGE PUBLICATIONS INC, 2022-11)
    OBJECTIVE: To use a systems paradigm to examine upper limb (UL) motor intervention elements driving biomarker and clinical measure improvement after stroke. METHODS: Databases were searched up to March 2022. Eligibility screening was completed by 2 authors. Studies using biomarkers and clinical measures pre- and post-upper limb intervention were included. Studies of adjunct interventions (eg, brain stimulation) were excluded. Cochrane Risk-of-Bias tools and Template for Intervention Description and Replication were used to rate studies. Studies were synthesized using a systems paradigm: intervention outcome was considered an emergent property of the systemic interactions of 4 intervention elements (demographics, type, quality, and dose) characterized by individual dimensions. RESULTS: Sixty-four studies (n = 1814 participants) containing 106 intervention groups (66 experimental; 40 control) were included. Combined biomarker and clinical outcomes defined 3 scenarios: restitution, mixed, and unchanged. The restitution scenario included more moderate-to-severely impaired participants in earlier recovery phases (<6 months). Interventions with graded difficulty were more frequently used in the restitution scenario compared with the unchanged scenario. No difference in quality or amount of therapy was identified when examining scenarios that demonstrated restitution compared to those that did not (mixed and unchanged). CONCLUSIONS: A systems paradigm may be one of many approaches to understand UL motor restitution. This review found no single element consistently delivered improvements in biomarkers and clinical measures in the examined intervention groups. Complex patterns formed by multiple interacting intervention elements were observed in participants with and without restitution.
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    Mood and Cognitive Trajectories Over the First Year after Mild Ischemic Stroke
    Ebaid, D ; Bird, LJ ; McCambridge, LJE ; Werden, E ; Bradshaw, J ; Cumming, T ; Tang, E ; Brodtmann, A (ELSEVIER, 2022-04)
    OBJECTIVES: Cognitive and mood dysfunction are major contributors to post-stroke disability. The longer-term trajectories of mood and cognition post-stroke remain unclear, as do which cognitive domains decline, improve, or remain stable after stroke, and in which patients. We aimed to characterize the cognitive trajectories of mild ischemic stroke survivors over one year compared to stroke-free controls, and to investigate whether symptoms of anxiety and depression were associated with cognitive function. MATERIALS AND METHODS: All participants were tested with a neuropsychological test battery at 3-months and 12-months post-stroke, assessing attention/processing speed, memory, visuospatial function, executive function, and language. Anxiety and depression symptomatology were also assessed at both timepoints. RESULTS: Stroke participants (N=126, mean age 68.44 years ±11.83, 87 males, median [Q1, Q3] admission NIHSS=2 [1, 4]) performed worse on cognitive tests and endorsed significantly higher depression and anxiety symptomatology than controls (N=40, mean age=68.82 years ±6.33, 25 males) at both timepoints. Mood scores were not correlated with cognitive performance. Stroke participants' scores trended higher across cognitive domains from 3- to 12-months but statistically significant improvement was only observed on executive function tasks. CONCLUSION: Stroke participants performed significantly worse than controls on all cognitive domains following mild ischemic stroke. Stroke participants only exhibited statistically significant improvement on executive function tasks between 3- and 12- months. Whilst anxiety and depression symptoms were higher in stroke participants, this was not correlated with cognitive performance. Further studies are needed to understand factors underlying cognitive recovery and decline after stroke.
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    Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide
    Liew, S-L ; Zavaliangos-Petropulu, A ; Schweighofer, N ; Jahanshad, N ; Lang, CE ; Lohse, KR ; Banaj, N ; Barisano, G ; Baugh, LA ; Bhattacharya, AK ; Bigjahan, B ; Borich, MR ; Boyd, LA ; Brodtmann, A ; Buetefisch, CM ; Byblow, WD ; Cassidy, JM ; Charalambous, CC ; Ciullo, V ; Conforto, AB ; Craddock, RC ; Dula, AN ; Egorova, N ; Feng, W ; Fercho, KA ; Gregory, CM ; Hanlon, CA ; Hayward, KS ; Holguin, JA ; Hordacre, B ; Hwang, DH ; Kautz, SA ; Khlif, MS ; Kim, B ; Kim, H ; Kuceyeski, A ; Lo, B ; Liu, J ; Lin, D ; Lotze, M ; MacIntosh, BJ ; Margetis, JL ; Mohamed, FB ; Nordvik, JE ; Petoe, MA ; Piras, F ; Raju, S ; Ramos-Murguialday, A ; Revill, KP ; Roberts, P ; Robertson, AD ; Schambra, HM ; Seo, NJ ; Shiroishi, MS ; Soekadar, SR ; Spalletta, G ; Stinear, CM ; Suri, A ; Tang, WK ; Thielman, GT ; Thijs, VN ; Vecchio, D ; Ward, NS ; Westlye, LT ; Winstein, CJ ; Wittenberg, GF ; Wong, KA ; Yu, C ; Wolf, SL ; Cramer, SC ; Thompson, PM (OXFORD UNIV PRESS, 2021-10-01)
    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.
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    The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain-behavior relationships after stroke
    Liew, S-L ; Zavaliangos-Petropulu, A ; Jahanshad, N ; Lang, CE ; Hayward, KS ; Lohse, KR ; Juliano, JM ; Assogna, F ; Baugh, LA ; Bhattacharya, AK ; Bigjahan, B ; Borich, MR ; Boyd, LA ; Brodtmann, A ; Buetefisch, CM ; Byblow, WD ; Cassidy, JM ; Conforto, AB ; Craddock, RC ; Dimyan, MA ; Dula, AN ; Ermer, E ; Etherton, MR ; Fercho, KA ; Gregory, CM ; Hadidchi, S ; Holguin, JA ; Hwang, DH ; Jung, S ; Kautz, SA ; Khlif, MS ; Khoshab, N ; Kim, B ; Kim, H ; Kuceyeski, A ; Lotze, M ; MacIntosh, BJ ; Margetis, JL ; Mohamed, FB ; Piras, F ; Ramos-Murguialday, A ; Richard, G ; Roberts, P ; Robertson, AD ; Rondina, JM ; Rost, NS ; Sanossian, N ; Schweighofer, N ; Seo, NJ ; Shiroishi, MS ; Soekadar, SR ; Spalletta, G ; Stinear, CM ; Suri, A ; Tang, WKW ; Thielman, GT ; Vecchio, D ; Villringer, A ; Ward, NS ; Werden, E ; Westlye, LT ; Winstein, C ; Wittenberg, GF ; Wong, KA ; Yu, C ; Cramer, SC ; Thompson, PM (WILEY, 2022-01)
    The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large-scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided.