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

Meer, Maurits P. A. van; Marel, Kajo van der; Otte, Willem M.; Sprenkel, Jan Willem Berkelbach van der; Dijkhuizen, Rick M.

doi:10.1038/jcbfm.2010.124

Cited by 85 publications

(104 citation statements)

References 13 publications

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“…These results provide further support for a structural connectivity mechanism underlying changes in functional connectivity. 23 The interhemispheric imbalance reported in the sensorimotor network is in accordance with findings from task-based fMRI and is the basis for the usage of noninvasive transcranial magnetic stimulation techniques for the treatment of patients with stroke. 2 However, it is yet to be determined how such stimulation affects the resting-state functional connectivity in patients with stroke, because most studies have made use of task-based connectivity techniques.…”

Section: September 2014supporting

confidence: 60%

The Value of Resting-State Functional Magnetic Resonance Imaging in Stroke

Ovadia-Caro

Margulies

Villringer

2014

Stroke

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In the acute phase of stroke, the use of imaging techniques aims to provide pathophysiological information concerning vascular patency, areas of hypoperfusion, and metabolic and structural damage. Based on such information, therapeutic decisions such as the administration of reperfusion medications are made. After the acute phase, brain plasticity and reorganization are the main mechanisms underlying functional recovery, and improvement is determined by functional adaptations of distributed brain networks mediated by connectivity.1 Accordingly, new therapeutic approaches, such as noninvasive brain stimulation, target the modulation of connectivity and network function. 2,3 At this stage, imaging-based biomarkers should reflect the status of cerebral networks. As the relevance of the network view of stroke becomes increasingly evident, 4 so does the usefulness of imaging techniques in the assessment of cerebral network function in clinical populations. Most notably is the use of resting-state functional MRI (rs-fMRI).rs-fMRI is a task-independent functional neuroimaging approach based on intrinsic low-frequency fluctuations (typically <0.1 Hz) in the blood oxygenation level-dependent (BOLD) signal. This signal can be used to compute the temporal correlations between spatially remote areas, termed: functional connectivity. In the healthy brain, functional connectivity is increased between areas that are part of the same functional network even in the absence of task. The resulting spatial patterns closely resemble the activation patterns identified during specific tasks, 5 and these networks are referred to as resting-state networks. 6 Thus, rs-fMRI provides an approach for detailed investigation of functional networks, as well as a more general method for assessing changes in intrinsic neuronal activity. Unlike task-based methods, measures of intrinsic functional connectivity allow for flexible post hoc analyses that probe multiple functional networks. Additionally, the minimal demands on the patient during the scanning session make the technique an optimal choice for clinical settings.rs-fMRI may offer the prospect of providing therapeutically useful information on both the focal vascular lesion and the connectivity-based reorganization and subsequent functional recovery. Here we provide an overview of recent applications of rs-fMRI to stroke diagnostics and prognostics and discuss future perspectives and considerations. We begin with methods used to characterize local alterations in acute stroke and proceed to describe studies of specific and general connectivity changes at various phases of the recovery process. For a detailed description of the studies reviewed here, see Table I in the online-only Data Supplement. Local Intrinsic BOLD Activity as a Measure of HypoperfusionCorrelation analyses based on the BOLD signal are thought to reflect neuronal synchronization. 7 However, the BOLD signal additionally contains information concerning local blood flow and oxygen consumption 8 and is, therefore, potentially...

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Section: September 2014supporting

confidence: 60%

The Value of Resting-State Functional Magnetic Resonance Imaging in Stroke

Ovadia-Caro

Margulies

Villringer

2014

Stroke

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“…It is well-documented in humans (2), non-human primates (3), cats (4), and rodents (5-7) that peripheral nerve injury can lead to expansion of neighboring cortical representation of peripheral regions within the affected (deprived) hemisphere (intrahemispheric neuroplasticity). Peripheral nerve injury and direct cortical lesions have been shown to also modify functional communication between cortical hemispheres (interhemispheric neuroplasticity) (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Specifically, peripheral inputs normally evoking neuronal responses in the contralateral hemisphere cause inappropriate functional responses in the ipsilateral hemisphere.…”

mentioning

confidence: 99%

Optogenetic-guided cortical plasticity after nerve injury

Downey

Bar‐Shir

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Peripheral nerve injury causes sensory dysfunctions that are thought to be attributable to changes in neuronal activity occurring in somatosensory cortices both contralateral and ipsilateral to the injury. Recent studies suggest that distorted functional response observed in deprived primary somatosensory cortex (S1) may be the result of an increase in inhibitory interneuron activity and is mediated by the transcallosal pathway. The goal of this study was to develop a strategy to manipulate and control the transcallosal activity to facilitate appropriate plasticity by guiding the cortical reorganization in a rat model of sensory deprivation. Since transcallosal fibers originate mainly from excitatory pyramidal neurons somata situated in laminae III and V, the excitatory neurons in rat S1 were engineered to express halorhodopsin, a light-sensitive chloride pump that triggers neuronal hyperpolarization. Results from electrophysiology, optical imaging, and functional MRI measurements are concordant with that within the deprived S1, activity in response to intact forepaw electrical stimulation was significantly increased by concurrent illumination of halorhodopsin over the healthy S1. Optogenetic manipulations effectively decreased the adverse inhibition of deprived cortex and revealed the major contribution of the transcallosal projections, showing interhemispheric neuroplasticity and thus, setting a foundation to develop improved rehabilitation strategies to restore cortical functions.recovery | amputation A lthough 20 million Americans suffer from peripheral nerve injury caused by trauma, metabolic, endocrine, and autoimmune disorders, there are few strategies to promote recovery. Surgical nerve repair and training of the injured limb are the classical rehabilitation approaches. Nevertheless, the clinical outcome in adults is generally poor, with persisting sensory dysfunction and pain (1).Recent evidence suggests that sensory dysfunctions caused by nerve injury should be attributable not only to the functional, cellular, and biochemical events occurring in peripheral nerve but also functional and anatomical changes occurring in cerebral cortical representations. It is well-documented in humans (2), non-human primates (3), cats (4), and rodents (5-7) that peripheral nerve injury can lead to expansion of neighboring cortical representation of peripheral regions within the affected (deprived) hemisphere (intrahemispheric neuroplasticity). Peripheral nerve injury and direct cortical lesions have been shown to also modify functional communication between cortical hemispheres (interhemispheric neuroplasticity) (8-19). Specifically, peripheral inputs normally evoking neuronal responses in the contralateral hemisphere cause inappropriate functional responses in the ipsilateral hemisphere. Previously, using singleunit electrophysiology recordings and juxtacellular labeling, it was shown that the inappropriate ipsilateral functional magnetic resonance imaging (fMRI) responses observed in deprived primary somatosensory cor...

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“…Owing to the limitation of the VSD technique, this study did not investigate involvement of prefrontal circuits or subcortical circuits. Other groups have used resting state fMRI to investigate brainwide network changes after stroke, which allows a more global and longitudinal investigation [100,148,149]. Although this is promising, the resting state frequencies are low and the algorithms used to calculate the network dynamics still need to be optimized for proper interpretation of these data.…”

Section: Optogenetic Interrogation Of Post-stroke Remapping and Recoverymentioning

confidence: 99%

Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

2016

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Stroke is a leading cause of death and disability in the USA, yet treatment options are very limited. Functional recovery can occur after stroke and is attributed, in part, to rewiring of neural connections in areas adjacent to or remotely connected to the infarct. A better understanding of neural circuit rewiring is thus an important step toward developing future therapeutic strategies for stroke recovery. Because stroke disrupts functional connections in peri-infarct and remotely connected regions, it is important to investigate brain-wide network dynamics during post-stroke recovery. Optogenetics is a revolutionary neuroscience tool that uses bioengineered lightsensitive proteins to selectively activate or inhibit specific cell types and neural circuits within milliseconds, allowing greater specificity and temporal precision for dissecting neural circuit mechanisms in diseases. In this review, we discuss the current view of post-stroke remapping and recovery, including recent studies that use optogenetics to investigate neural circuit remapping after stroke, as well as optogenetic stimulation to enhance stroke recovery. Multimodal approaches employing optogenetics in conjunction with other readouts (e.g., in vivo neuroimaging techniques, behavior assays, and next-generation sequencing) will advance our understanding of neural circuit reorganization during post-stroke recovery, as well as provide important insights into which brain circuits to target when designing brain stimulation strategies for future clinical studies.

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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

Cited by 85 publications

References 13 publications

The Value of Resting-State Functional Magnetic Resonance Imaging in Stroke

The Value of Resting-State Functional Magnetic Resonance Imaging in Stroke

Optogenetic-guided cortical plasticity after nerve injury

Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

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