Recovery of Sensorimotor Function after Experimental Stroke Correlates with Restoration of Resting-State Interhemispheric Functional Connectivity

Abstract

Despite the success of functional imaging to map changes in brain activation patterns after stroke, spatiotemporal dynamics of cerebral reorganization in correlation with behavioral recovery remain incompletely characterized. Here, we applied resting-state functional magnetic resonance imaging (rs-fMRI) together with behavioral testing to longitudinally assess functional connectivity within neuronal networks, in relation to changes in associated function after unilateral stroke in rats. Our specific goals were (1) to identify temporal alterations in functional connectivity within the bilateral cortical sensorimotor system and (2) to elucidate the relationship between those alterations and changes in sensorimotor function. Our study revealed considerable loss of functional connectivity between ipsilesional and contralesional primary sensorimotor cortex regions, alongside significant sensorimotor function deficits in the first days after stroke. The interhemispheric functional connectivity restored in the following weeks, but remained significantly reduced up to 10 weeks after stroke in animals with lesions that comprised subcortical and cortical tissue, whereas transcallosal neuroanatomical connections were preserved. Intrahemispheric functional connectivity between primary somatosensory and motor cortex areas was preserved in the lesion border zone and moderately enhanced contralesionally. The temporal pattern of changes in functional connectivity between bilateral primary motor and somatosensory cortices correlated significantly with the evolution of sensorimotor function scores. Our study (1) demonstrates that poststroke loss and recovery of sensorimotor function is associated with acute deterioration and subsequent retrieval of interhemispheric functional connectivity within the sensorimotor system and (2) underscores the potential of rs-fMRI to assess spatiotemporal characteristics of functional brain reorganization that may underlie behavioral recovery after brain injury.

Correspondence between Altered Functional and Structural Connectivity in the Contralesional Sensorimotor Cortex after Unilateral Stroke in Rats: A Combined Resting-State Functional MRI and Manganese-Enhanced MRI Study

“…In agreement with our previous study (van Meer et al, 2010), interhemispheric functional connectivity…”

“…In line with our previous study (van Meer et al, 2010), we found a significant increase in intrahemispheric functional connectivity within the contralesional sensorimotor cortex in rats with a relatively large unilateral infarction in the opposite (ipsilesional) sensorimotor network. In addition, we detected increased accumulation of the neuronal tracer manganese within the contralesional sensorimotor cortex of rats with large unilateral ischemic lesions, which suggests that the increase in functional connectivity is related to stronger local neuroanatomical association.…”

“…Preprocessing of rs-fMRI data included motion correction, spatial smoothing, and linear regression, as described previously (van Meer et al, 2010). Subsequently, low-frequency BOLD fluctuations were extracted by applying a band-pass filter with 0.01 < f < 0.1 Hz.…”

“…Task-or stimulus-induced functional imaging studies in stroke patients and animal models have provided evidence for shifts of activation patterns in ipsilesional and contralesional sensorimotor cortices in relation to sensorimotor recovery (Calautti and Baron, 2003;Dijkhuizen et al, 2003), which may be based on unmasking or strengthening of existing pathways and/or by formation of new connections (Nudo, 1999;Dancause, 2006). Resting-state functional magnetic resonance imaging (MRI) (rs-fMRI), which assesses the temporal correlation of spontaneous lowfrequency blood oxygenation level-dependent (BOLD) signals between brain areas as a measure of functional connectivity (Biswal et al, 1995), has recently showed that patients and rats with a unilateral infarction exhibit initial loss and subsequent restitution of interhemispheric functional connectivity, in parallel to changes in functional status (He et al, 2007;van Meer et al, 2010). Furthermore, increased intrahemispheric functional connectivity in the contralesional primary sensorimotor cortex was observed in rats with large unilateral lesions (van Meer et al, 2010).…”

“…Resting-state functional magnetic resonance imaging (MRI) (rs-fMRI), which assesses the temporal correlation of spontaneous lowfrequency blood oxygenation level-dependent (BOLD) signals between brain areas as a measure of functional connectivity (Biswal et al, 1995), has recently showed that patients and rats with a unilateral infarction exhibit initial loss and subsequent restitution of interhemispheric functional connectivity, in parallel to changes in functional status (He et al, 2007;van Meer et al, 2010). Furthermore, increased intrahemispheric functional connectivity in the contralesional primary sensorimotor cortex was observed in rats with large unilateral lesions (van Meer et al, 2010).…”