BOLD study of stimulation-induced neural activity and resting-state connectivity in medetomidine-sedated rat

Zhao, Fuqiang; Zhao, Tiejun; Zhou, Lei; Wu, Qisong; Hu, Xiaoping

doi:10.1016/j.neuroimage.2007.07.063

Cited by 181 publications

(216 citation statements)

References 67 publications

(102 reference statements)

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“…Dexmedetomidine, an α 2 -agonist routinely used in human medical practice, produces dose-dependent sedative effects along with analgesia, muscle relaxation, and anxiolysis. It was recently introduced for longitudinal functional MRI and resting state fMRI studies in rodents (15,52). However, the sedative effect of medetomidine is reduced with constant infusion of medetomidine alone, and a stepwise dose increase has been suggested to maintain stable sedation (17).…”

Section: Discussionmentioning

confidence: 99%

Rat brains also have a default mode network

Zou

et al. 2012

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

530

571

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The default mode network (DMN) in humans has been suggested to support a variety of cognitive functions and has been implicated in an array of neuropsychological disorders. However, its function (s) remains poorly understood. We show that rats possess a DMN that is broadly similar to the DMNs of nonhuman primates and humans. Our data suggest that, despite the distinct evolutionary paths between rodent and primate brain, a well-organized, intrinsically coherent DMN appears to be a fundamental feature in the mammalian brain whose primary functions might be to integrate multimodal sensory and affective information to guide behavior in anticipation of changing environmental contingencies.functional MRI | resting state | intrinsic activity | connectivity | spontaneous fluctuation I n the absence of an immediate need for goal-directed attention to the surrounding environment, our minds wander from recollection of past happenings to imagination of future events. Neuroimaging studies have consistently identified a set of interconnected brain areas that becomes less active during attentiondemanding cognitive tasks (1). This so-called default mode network (DMN) is posited to play a fundamental role in brain organization and supports a variety of self-referential functions such as understanding others' mental state, recollection and imagination (2), conceptual processing (3), and even in the sustenance of conscious awareness (4). Many of these functions have been considered to be unique to humans. Intriguingly, similar coherent structures have been shown to exist in anesthetized macaque monkeys and chimpanzees (5, 6). Furthermore, the functions of the default network are disrupted in such neuropsychological disorders as schizophrenia, Alzheimer's disease, and autism (7-9), underscoring the clear and critical need for further investigating the neurobiological basis of DMN using animal models.The evolutionary clade of rodents is about 35 million years earlier than that of old world monkeys and about 60 million years earlier than humans (10). Although many of the structures and functions of subcortical nuclei are conserved across these three species, the neocortex, in particular the "association" cortex, has extensively expanded in the primate as a result of evolutionary pressure, which is considered to be crucial in the development of higher cognitive and behavioral functions (10, 11). On the other hand, such structures as cingulate cortex, prefrontal cortex, and hippocampal formation, all of which are critical elements of the DMN, are also present in rodents (11). Given the distant evolutionary paths between rodent and primate brain, an intriguing question arises: Does the rat possess a similar DMN? Such a network, once demonstrated, would not only suggest that an operational DMN is a common feature in the mammalian brain, perhaps induced via parallel evolution as a result of natural selection, it would also offer a novel platform to explore the physiological basis and behavioral significance of the DMN. Such a demonstratio...

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Section: Discussionmentioning

confidence: 99%

Rat brains also have a default mode network

Zou

et al. 2012

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

530

571

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“…Nociceptive stimuli have been shown to reliably evoke this intriguing negative fMRI responses in the rat striatum under alphachloralose anesthesia, 2,5,6,10 medetomidine sedation, 4 or medetomidine combined with light isoflurane (0.4%) anesthesia. 3 This stimulation model has potential to serve as a functional imaging marker for striatal functional integrity for various types of preclinical applications in rodents.…”

Section: Introductionmentioning

confidence: 98%

“…1 It plays a pivotal role in several neurodegenerative disorders and regulating motor behavior. Recent reports showed that unilateral noxious forepaw electrical stimulation in rats evoked sustained negative blood oxygenation level dependent (BOLD), cerebral blood flow (CBF), and cerebral blood volume (CBV) functional magnetic resonance imaging (fMRI) responses in the bilateral striatum with no significant difference between two hemispheres, [2][3][4][5][6] while the neuronal spike and c-Fos activities increased. 6 This negative response has also been observed in epileptic rats during whisker stimulation 7 or normal rats during direct nerve stimulation.…”

Section: Introductionmentioning

confidence: 99%

“…Contralateral CPu (cCPu) response was not recorded because of our hardware limitation and the fact that no difference was detected between the two hemispheres in this model. [2][3][4][5][6] To investigate whether the striatal negative fMRI response can serve as a marker for striatal functional integrity, we used stimulation of 10 mA, 3 milliseconds pulse width, and 12 Hz in two groups of rats underwent 20-and 45-minute middle cerebral artery occlusion (MCAO) and followed the fMRI responses up to 28 days.…”

Section: Introductionmentioning

confidence: 99%

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Imaging Neurovascular Function and Functional Recovery after Stroke in the Rat Striatum Using Forepaw Stimulation

Shih

Huang

Lai

et al. 2014

J Cereb Blood Flow Metab

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Negative functional magnetic resonance imaging (fMRI) response in the striatum has been observed in several studies during peripheral sensory stimulation, but its relationship between local field potential (LFP) remains to be elucidated. We performed cerebral blood volume (CBV) fMRI and LFP recordings in normal rats during graded noxious forepaw stimulation at nine stimulus pulse widths. Albeit high LFP-CBV correlation was found in the ipsilateral and contralateral sensory cortices (r ¼ 0.89 and 0.95, respectively), the striatal CBV responses were neither positively, nor negatively correlated with LFP (r ¼ 0.04), demonstrating that the negative striatal CBV response is not originated from net regional inhibition. To further identify whether this negative CBV response can serve as a marker for striatal functional recovery, two groups of rats (n ¼ 5 each) underwent 20-and 45-minute middle cerebral artery occlusion (MCAO) were studied. No CBV response was found in the ipsilateral striatum in both groups immediately after stroke. Improved striatal CBV response was observed on day 28 in the 20-minute MCAO group compared with the 45-minute MCAO group (Po0.05). This study shows that fMRI signals could differ significantly from LFP and that the observed negative CBV response has potential to serve as a marker for striatal functional integrity in rats.

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“…The sensory and motor areas are strongly connected across hemispheres via the corpus callosum and exhibit high BOLD correlation when typical ''steady-state'' analysis methods are used (Pawela et al, 2008;Williams et al, 2010;Zhao et al, 2008). In contrast, the left and right caudate putamen (CP) are only indirectly connected but still exhibit BOLD-based functional connectivity (Williams et al, 2010;Zhao et al, 2008). The caudate also receives input from somatosensory cortex, but a signal from the two areas is usually not correlated in functional connectivity studies.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Properties of Functional Connectivity in the Rodent

Keilholz

Magnuson²,

Pan³

et al. 2013

Brain Connectivity

130

161

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Functional connectivity mapping with resting-state magnetic resonance imaging (MRI) has become an immensely powerful technique that provides insight into both normal cognitive function and disruptions linked to neurological disorders. Traditionally, connectivity is mapped using data from an entire scan (minutes), but it is well known that cognitive processes occur on much shorter time scales (seconds). Recent studies have demonstrated that the correlation between the blood oxygenation level-dependent (BOLD) MRI signal from different areas varies over time, motivating a further exploration of these fluctuations in apparent connectivity. However, it has also been shown that similar changes in correlation can arise when the timing relationships between voxels are randomized (Handwerker et al., 2012). In this work, we show that functional connectivity in the anesthetized rat exhibits dynamic properties that are similar to those previously observed in awake humans (Chang and Glover, 2010) and anesthetized monkeys (Hutchison et al., 2012). Sliding window correlation between BOLD time courses obtained from bilateral cortical and subcortical regions of interest results in periods of variable positive and negative correlation for most pairs of areas except homologous areas in opposite hemispheres, which exhibit a primarily positive correlation. A comparison with sliding window correlation of randomly matched time courses suggests that with the exception of homologous areas and sensorimotor connections, the dynamics cannot be distinguished from random fluctuations in correlation over time, supporting the idea that some of these dynamic patterns may be due to inherent properties of the signal rather than variations in neural coherence. Within the pairs of areas where the dynamics are most different from those of randomly matched time courses, ten common patterns of connectivity are identified, and their occurrence as a function of time is plotted for all animals. The observation of time-varying correlation in the rodent model will facilitate the future multimodal experiments needed to determine whether the changes in apparent connectivity are linked to underlying neural variability.

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BOLD study of stimulation-induced neural activity and resting-state connectivity in medetomidine-sedated rat

Cited by 181 publications

References 67 publications

Rat brains also have a default mode network

Rat brains also have a default mode network

Imaging Neurovascular Function and Functional Recovery after Stroke in the Rat Striatum Using Forepaw Stimulation

Dynamic Properties of Functional Connectivity in the Rodent

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