title: Enhanced Thalamic Functional Connectivity with No fMRI Responses to Affected Forelimb Stimulation in Stroke-Recovered Rats.
abstract: Neurological recovery after stroke has been extensively investigated to provide better understanding of neurobiological mechanism, therapy, and patient management. Recent advances in neuroimaging techniques, particularly functional MRI (fMRI), have widely contributed to unravel the relationship between the altered neural function and stroke-affected brain areas. As results of previous investigations, the plastic reorganization and/or gradual restoration of the hemodynamic fMRI responses to neural stimuli have been suggested as relevant mechanisms underlying the stroke recovery process. However, divergent study results and modality-dependent outcomes have clouded the proper interpretation of variable fMRI signals. Here, we performed both evoked and resting state fMRI (rs-fMRI) to clarify the link between the fMRI phenotypes and post-stroke functional recovery. The experiments were designed to examine the altered neural activity within the contra-lesional hemisphere and other undamaged brain regions using rat models with large unilateral stroke, which despite the severe injury, exhibited nearly full recovery at ∼6 months after stroke. Surprisingly, both blood oxygenation level-dependent and blood volume-weighted (CBVw) fMRI activities elicited by electrical stimulation of the stroke-affected forelimb were completely absent, failing to reveal the neural origin of the behavioral recovery. In contrast, the functional connectivity maps showed highly robust rs-fMRI activity concentrated in the contra-lesional ventromedial nucleus of thalamus (VM). The negative finding in the stimuli-induced fMRI study using the popular rat middle cerebral artery model denotes weak association between the fMRI hemodynamic responses and neurological improvement. The results strongly caution the indiscreet interpretation of stroke-affected fMRI signals and demonstrate rs-fMRI as a complementary tool for efficiently characterizing stroke recovery.
authors.affiliation: Department of Radiology, ASAN Medical Center, University of Ulsan College of MedicineUlsan, South Korea; ASAN Institute for Life Sciences, ASAN Medical Center, University of Ulsan College of MedicineUlsan, South Korea; Department of Bio and Brain Engineering, Korea Advanced Institute of Science and TechnologyDaejeon, South Korea; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, BostonMA, USA.
authors.forename: Woo H
authors.initials: WH
authors.lastname: Shim
authors.affiliation: Department of Radiology, ASAN Medical Center, University of Ulsan College of MedicineUlsan, South Korea; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, BostonMA, USA.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Suh
authors.affiliation: Department of Radiology, ASAN Medical Center, University of Ulsan College of Medicine Ulsan, South Korea.
authors.forename: Jeong K
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology Daejeon, South Korea.
authors.forename: Jaeseung
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston MA, USA.
authors.forename: Young R
authors.initials: YR
authors.lastname: Kim
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005552:Forelimb; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051381:Rats; D020127:Recovery of Function / Q000502:physiology*; D020521:Stroke / Q000503:physiopathology*; D013787:Thalamic Nuclei / Q000503:physiopathology*
keywords: plastic reorganization; rat; resting state fMRI; stimulus-induced fMRI; stroke recovery