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Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime.

ABSTRACT: Neural activity is closely followed by a localised change in cerebral blood flow, a process termed neurovascular coupling. These hemodynamic changes form the basis of contrast in functional magnetic resonance imaging (fMRI) and are used as a correlate for neural activity. Anesthesia is widely employed in animal fMRI and neurovascular studies, however anesthetics are known to profoundly affect neural and vascular physiology, particularly in mice. Therefore, we investigated the efficacy of a novel 'modular' anesthesia that combined injectable (fentanyl-fluanisone/midazolam) and volatile (isoflurane) anesthetics in mice. To characterize sensory-evoked cortical hemodynamic responses, we used optical imaging spectroscopy to produce functional maps of changes in tissue oxygenation and blood volume in response to mechanical whisker stimulation. Following fine-tuning of the anesthetic regime, stimulation elicited large and robust hemodynamic responses in the somatosensory cortex, characterized by fast arterial activation, increases in total and oxygenated hemoglobin, and decreases in deoxygenated hemoglobin. Overall, the magnitude and speed of evoked hemodynamic responses under anesthesia resembled those in the awake state, indicating that the novel anesthetic combination significantly minimizes the impact of anesthesia. Our findings have broad implications for both neurovascular research and longitudinal fMRI studies that increasingly require the use of genetically engineered mice.

SUBMITTER: Sharp PS

PROVIDER: S-EPMC4517464 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime.

Sharp Paul S PS Shaw Kira K Shaw Kira K Boorman Luke L Harris Samuel S Kennerley Aneurin J AJ Azzouz Mimoun M Berwick Jason J

Scientific reports 20150728

Neural activity is closely followed by a localised change in cerebral blood flow, a process termed neurovascular coupling. These hemodynamic changes form the basis of contrast in functional magnetic resonance imaging (fMRI) and are used as a correlate for neural activity. Anesthesia is widely employed in animal fMRI and neurovascular studies, however anesthetics are known to profoundly affect neural and vascular physiology, particularly in mice. Therefore, we investigated the efficacy of a novel ...[more]

PMID: 26218081

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Project description:Purpose: To extend our knowledge of the functional linkages between visual fatigue and regional cerebral prefrontal cortex (PFC) oxygenation, we measured time related hemodynamic changes over the right dorsolateral prefrontal cortex (dlPFC) during convergence load under conflicting stimulus-to-accommodation and stimulus-to-vergence eye movements with and without concurrent mental load. Methods: Twenty healthy participants with a median age of 28 years (range: 18-44 years) fixated upon a vertical bar presented separately to the left and right eyes, using polarized filters, during four counterbalanced 10-min periods: (i) no accommodation/vergence conflict (Control, Ctrl); (ii) added convergence load and accommodation/vergence conflict (Conv); (iii) added cognitive load only (Cog) and; (iv) a combination of added cognitive and convergence load and accommodation/vergence conflict (Cc). Viewing distance was 65 cm. Non-invasive measurements of hemodynamic activity over the dlPFC were quantified by functional near-infrared spectroscopy (fNIRS). During the two-convergence load conditions, the horizontal disparity of the two bars varied dynamically from no disparity to a disparity set 20% below the individual threshold for diplopia. Cognitive load was induced by the n-back-2 test which required the subject to memorize and recall the changing colors of the horizontal bars and decide when a given color was the same as that occurring two colors previously. fNIRS data were averaged over 10-s windows centered at 0, 2, 4, 6, 8, and 10 min of each task, subtracted from a 20-s baseline window immediately preceding the visual task, and then represented as changes in oxygenated hemoglobin (?HbO2), deoxygenated hemoglobin (?HHb) and total hemoglobin (?tHb). Results: Linear mixed model analyses showed that hemodynamic activity was systematically influenced by time (p < 0.001). The group-averaged time-related level of change across the viewing conditions did not differ when compared with one another (p > 0.05). Larger convergence eye-movement responses under conflicting stimulus-to-accommodation, and stimulus-to-vergence over time, increased ?HbO2 and ?tHb only in condition Cc and after 8 min of task time (p < 0.10 for min-6 and min-8: p < 0.05 for min-10). Discussion: Collectively, our data suggest that HbO2, HHb, and tHb, recorded over the dlPFC with fNIRS, can be used to assay the degree to which supervisory oculomotor control processes are activated during visually deficient near work.

Dataset Information

Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime.

Publications

Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime.

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