Dataset Information

FMRI in the awake marmoset: somatosensory-evoked responses, functional connectivity, and comparison with propofol anesthesia.

ABSTRACT: Functional neuroimaging in animal models is essential for understanding the principles of neurovascular coupling and the physiological basis of fMRI signals that are widely used to study sensory and cognitive processing in the human brain. While hemodynamic responses to sensory stimuli have been characterized in humans, animal studies are able to combine very high resolution imaging with invasive measurements and pharmacological manipulation. To date, most high-resolution studies of neurovascular coupling in small animals have been carried out in anesthetized rodents. Here we report fMRI experiments in conscious, awake common marmosets (Callithrix jacchus), and compare responses to animals anesthetized with propofol. In conscious marmosets, robust BOLD fMRI responses to somatosensory stimulation of the forearm were found in contralateral and ipsilateral regions of the thalamus, primary (SI) and secondary (SII) somatosensory cortex, and the caudate nucleus. These responses were markedly stronger than those in anesthetized marmosets and showed a monotonic increase in the amplitude of the BOLD response with stimulus frequency. On the other hand, anesthesia significantly attenuated responses in thalamus, SI and SII, and abolished responses in caudate and ipsilateral SI. Moreover, anesthesia influenced several other aspects of the fMRI responses, including the shape of the hemodynamic response function and the interareal (SI-SII) spontaneous functional connectivity. Together, these findings demonstrate the value of the conscious, awake marmoset model for studying physiological responses in the somatosensory pathway, in the absence of anesthesia, so that the data can be compared most directly to fMRI in conscious humans.

SUBMITTER: Liu JV

PROVIDER: S-EPMC3778909 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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fMRI in the awake marmoset: somatosensory-evoked responses, functional connectivity, and comparison with propofol anesthesia.

Liu Junjie V JV Hirano Yoshiyuki Y Nascimento George C GC Stefanovic Bojana B Leopold David A DA Silva Afonso C AC

NeuroImage 20130406

Functional neuroimaging in animal models is essential for understanding the principles of neurovascular coupling and the physiological basis of fMRI signals that are widely used to study sensory and cognitive processing in the human brain. While hemodynamic responses to sensory stimuli have been characterized in humans, animal studies are able to combine very high resolution imaging with invasive measurements and pharmacological manipulation. To date, most high-resolution studies of neurovascula ...[more]

PMID: 23571417

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Project description:IntroductionCorrelated low-frequency fluctuations of resting-state functional magnetic resonance imaging (rsfMRI) signals have been widely used for inferring intrinsic brain functional connectivity (FC). In animal studies, accurate estimate of anesthetic effects on rsfMRI signals is demanded for reliable interpretations of FC changes. We have previously shown that inter-regional FC can reliably delineate local millimeter-scale circuits within digit representations of primary somatosensory cortex (S1) subregions (areas 3a, 3b, and 1) in monkeys under isoflurane anesthesia. The goals of this study are to determine (1) the general effects of isoflurane on rsfMRI signals in the S1 circuit and (2) whether the effects are functional- and regional- dependent, by quantifying the relationships between isoflurane levels, power and inter-regional correlation coefficients in digit and face regions of distinct S1 subregions.MethodsFunctional MRI data were collected from male adult squirrel monkeys at three different isoflurane levels (1.25%, 0.875%, and 0.5%). All scans were acquired on a 9.4T magnet with a 3-cm-diameter surface transmit-receive coil centered over the S1 cortex. Power and seed-based inter-regional functional connectivity analyses were subsequently performed.ResultsAs anesthesia level increased, we observed (1) diminishing amplitudes of signal fluctuations, (2) reduced power of fluctuations in the low-frequency band used for connectivity measurements, (3) decreased inter-voxel connectivity around seed regions, and (4) weakened inter-regional FC across all pairs of regions of interest (digit-to-digit). The low-frequency power measures derived from rsfMRI signals from control muscle regions, however, did not exhibit any isoflurane level-related changes. Within the isoflurane dosage range we tested, the inter-regional functional connectivity differences were still detectable, and the effects of isoflurane did not differ across region-of-interest (ROI) pairs.ConclusionOur data demonstrate that isoflurane induced similar dose-dependent suppressive effects on the power of rsfMRI signals and local fine-scale FC across functionally related but distinct S1 subregions.

Project description:The exact neurophysiological basis of chronic tinnitus, which affects 10-15% of the population, remains unknown and is controversial at many levels. It is an open question whether phantom sound perception results from increased central neural gain or not, a crucial question for any future therapeutic intervention strategies for tinnitus. We performed a comprehensive study of mild hearing-impaired participants with and without tinnitus, excluding participants with co-occurrences of hyperacusis. A right-hemisphere correlation between tinnitus loudness and auditory perceptual difficulty was observed in the tinnitus group, independent of differences in hearing thresholds. This correlation was linked to reduced and delayed sound-induced suprathreshold auditory brain responses (ABR wave V) in the tinnitus group, suggesting subsided rather than exaggerated central neural responsiveness. When anatomically predefined auditory regions of interest were analysed for altered sound-evoked BOLD fMRI activity, it became evident that subcortical and cortical auditory regions and regions involved in sound detection (posterior insula, hippocampus), responded with reduced BOLD activity in the tinnitus group, emphasizing reduced, rather than increased, central neural gain. Regarding previous findings of evoked BOLD activity being linked to positive connectivities at rest, we additionally analysed r-fcMRI responses in anatomically predefined auditory regions and regions associated with sound detection. A profound reduction in positive interhemispheric connections of homologous auditory brain regions and a decline in the positive connectivities between lower auditory brainstem regions and regions involved in sound detection (hippocampus, posterior insula) were observed in the tinnitus group. The finding went hand-in-hand with the emotional (amygdala, anterior insula) and temporofrontal/stress-regulating regions (prefrontal cortex, inferior frontal gyrus) that were no longer positively connected with auditory cortex regions in the tinnitus group but were instead positively connected to lower-level auditory brainstem regions. Delayed sound processing, reduced sound-evoked BOLD fMRI activity and altered r-fcMRI in the auditory midbrain correlated in the tinnitus group and showed right hemisphere dominance as did tinnitus loudness and perceptual difficulty. The findings suggest that reduced central neural gain in the auditory stream may lead to phantom perception through a failure to energize attentional/stress-regulating networks for contextualization of auditory-specific information. Reduced auditory-specific information flow in tinnitus has until now escaped detection in humans, as low-level auditory brain regions were previously omitted from neuroimaging studies.Trial registrationGerman Clinical Trials Register DRKS0006332.

Project description:BackgroundDisconnected consciousness describes a state in which subjective experience (i.e., consciousness) becomes isolated from the external world. It appears frequently during sleep or sedation, when subjective experiences remain vivid but are unaffected by external stimuli. Traditional methods of differentiating connected and disconnected consciousness, such as relying on behavioral responsiveness or on post-anesthesia reports, have demonstrated limited accuracy: unresponsiveness has been shown to not necessarily equate to unconsciousness and amnesic effects of anesthesia and sleep can impair explicit recollection of events occurred during sleep/sedation. Due to these methodological challenges, our understanding of the neural mechanisms underlying sensory disconnection remains limited.MethodsTo overcome these methodological challenges, we employ a distinctive strategy by combining a serial awakening paradigm with auditory stimulation during mild propofol sedation. While under sedation, participants are systematically exposed to auditory stimuli and questioned about their subjective experience (to assess consciousness) and their awareness of the sounds (to evaluate connectedness/disconnectedness from the environment). The data collected through interviews are used to categorize participants into connected and disconnected consciousness states. This method circumvents the requirement for responsiveness in assessing consciousness and mitigates amnesic effects of anesthesia as participants are questioned while still under sedation. Functional MRI data are concurrently collected to investigate cerebral activity patterns during connected and disconnected states, to elucidate sensory disconnection neural gating mechanisms. We examine whether this gating mechanism resides at the thalamic level or results from disruptions in information propagation to higher cortices. Furthermore, we explore the potential role of slow-wave activity (SWA) in inducing disconnected consciousness by quantifying high-frequency BOLD oscillations, a known correlate of slow-wave activity.DiscussionThis study represents a notable advancement in the investigation of sensory disconnection. The serial awakening paradigm effectively mitigates amnesic effects by collecting reports immediately after regaining responsiveness, while still under sedation. Ultimately, this research holds the potential to understand how sensory gating is achieved at the neural level. These biomarkers might be relevant for the development of sensitive anesthesia monitoring to avoid intraoperative connected consciousness and for the assessment of patients suffering from pathologically reduced consciousness.Clinical trial registrationEuropean Union Drug Regulating Authorities Clinical Trials Database (EudraCT), identifier 2020-003524-17.

Dataset Information

FMRI in the awake marmoset: somatosensory-evoked responses, functional connectivity, and comparison with propofol anesthesia.

Publications

fMRI in the awake marmoset: somatosensory-evoked responses, functional connectivity, and comparison with propofol anesthesia.

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