Modulation of the BOLD-response in early recovery from sensorimotor stroke Ferdinand Binkofski, MD; and Rüdiger J. Seitz, MD Abstract—Background: The BOLD signal in functional MRI (fMRI) is closely related to neural activity. Objective: To investigate if this relationship is disrupted after ischemic stroke. Methods: BOLD activity during tactile exploration of objects was measured with fMRI at 1 week (subacute), 2 to 4 weeks (early chronic), and after 1 month (chronic) after the first completed brain infarction affecting the sensorimotor cortex in eight patients. Functional integrity of the motor cortical output system was assessed with transcranial magnetic stimulation (TMS). Results: Early after infarction the BOLD-response occurred in the adjacent cortical vicinity related to finger movements of the affected hand. However, during the early chronic stage there was a transient lack of this activation despite clinical improvement of hand function and preserved motor evoked potentials. The BOLD activity reappeared after further improvement in the chronic stage. Conclusions: Our findings suggest a transient hemodynamic-electrical decoupling in the post-ischemic cerebral cortex during the early phase of spontaneous clinical recovery. NEUROLOGY 2004;63:1223–1229 Functional imaging studies in patients who have re- covered from brain infarction showed abnormal corti- cal activations resembling reorganization of cortical representations in animal experiments. A posterior shift of the activation related to motor activation was observed. 1,2 Furthermore, there was evidence that ac- tivation related to sensorimotor activity occurred in somatosensory cortex after infarction of motor cor- tex, while activation in motor cortex was observed after infarction of somatosensory cortex. 3 Such find- ings were suited to suggest a local reorganization of cortical representations by the plastic capacity of the perilesional neural machinery. 4 However, there were also reports that in infarcts of the sensorimotor cor- tex, there may be a lack of movement-related activa- tion, although the corticospinal tract and the afferent somatosensory tract were largely functional as assessed by evoked potential and metabolic stud- ies. 5,6 Similarly, diminished rCBF increases caused by sensorimotor stimulation have been reported af- ter transient cortical ischemic attacks and after sub- cortical stroke. 7,8 Possibly, these observations corresponded to the uncoupling of rCBF (no re- sponse) from rCMRGlu (persistent response) which was explained by an ischemia-induced inhibition of the neuronal nitric oxide synthetase that mediates the hemodynamic response. 9 Furthermore, in addition to the abnormalities in the affected hemisphere, there is good evidence from functional imaging showing that the motor system in the contralesional hemisphere plays an important role in postischemic reorganization. 10-12 Active and passive sensorimotor tasks were reported to show a largely bilateral activation pattern as recovery pro- gressed. 13,14 Remarkably, the more symmetric the ac- tivations in both cerebral hemispheres were, the greater was the white matter affection and the worse the clinical outcome. 15,16 However, the symmetry of the activations in motor cortex are only meaningful as a marker for reorganization, if the relation of the hemodynamic response to the underlying neural ac- tivity is valid. We studied the function of the perilesional brain tissue surrounding an ischemic infarct by fMRI dur- ing tactile object exploration. Tactile exploration of objects is an over-learned activity acquired during infancy. 17 It is made of fractionated movements of the fingers that scan the objects with high profi- ciency to sample sensory information. In previous studies we have shown that tactile exploration en- gages a well defined cortical circuit both in healthy subjects and patients with cortical and subcortical stroke. 6,8,18,19 Because in this study we were inter- ested in a robust hemodynamic response in the sen- sorimotor cortex, we employed this activation paradigm to study the dynamics of changes during the first weeks after stroke. We studied patients with a first completed ischemic stroke affecting the sensorimotor cortex, who presented with initial hemiparesis and loss of hand function. We supple- mented fMRI with transcranial magnetic stimula- tion (TMS) assessment of the motor cortical output From the Department of Neurology (Dr. Binkofski), University Hospital Schleswig-Holstein, Campus Lübeck, Germany; Neuroimage Nord (Dr. Binkofski), University Hospital Eppendorf, Hamburg, Germany; and Department of Neurology (Dr. Seitz), University Hospital Düsseldorf, Germany. This study was supported by grants of the Sonderforschungsbereich 194 (A13, A16), the Bundesministerium für Bildung und Forschung (Kompetenznetz Schlaganfall), BMBF Neuroimagingzentrum GF GO 1337400, Brain Imaging Center West (BMBF, TP4), Biomedizinisches Forschungszentrum of the Heinrich-Heine-University Düsseldorf, and Volkswagenstiftung I/79006. Received December 29, 2003. Accepted in final form May 25, 2004. Address correspondence and reprint requests to Dr. Ferdinand Binkofski, Department of Neurology, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23539 Lübeck, Germany; e-mail: binkofski.f@neuro.mu-luebeck.de Copyright © 2004 by AAN Enterprises, Inc. 1223