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Physiological and pathological brain activation in the anesthetized rat produces hemodynamic-dependent cortical temperature increases that can confound the BOLD fMRI signal

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  • Samuel S Harris
  • Luke W Boorman
  • Devashish Das
  • Aneurin J Kennerley
  • Paul S Sharp
  • Chris Martin
  • Peter Redgrave
  • Theodore H Schwartz
  • Jason Berwick


Publication details

JournalFrontiers in Neuroscience
DateAccepted/In press - 20 Jul 2018
DatePublished (current) - 14 Aug 2018
Issue numberAUG
Number of pages11
Pages (from-to)550
Original languageEnglish


Anesthetized rodent models are ubiquitous in pre-clinical neuroimaging studies. However, because the associated cerebral morphology and experimental methodology results in a profound negative brain-core temperature differential, cerebral temperature changes during functional activation are likely to be principally driven by local inflow of fresh, core-temperature, blood. This presents a confound to the interpretation of blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data acquired from such models, since this signal is also critically temperature-dependent. Nevertheless, previous investigation on the subject is surprisingly sparse. Here, we address this issue through use of a novel multi-modal methodology in the urethane anesthetized rat. We reveal that sensory stimulation, hypercapnia and recurrent acute seizures induce significant increases in cortical temperature that are preferentially correlated to changes in total hemoglobin concentration (Hbt), relative to cerebral blood flow and oxidative metabolism. Furthermore, using a phantom-based evaluation of the effect of such temperature changes on the BOLD fMRI signal, we demonstrate a robust inverse relationship between both variables. These findings suggest that temperature increases, due to functional hyperemia, should be accounted for to ensure accurate interpretation of BOLD fMRI signals in pre-clinical neuroimaging studies.

Bibliographical note

© 2018 Harris, Boorman, Das, Kennerley, Sharp, Martin, Redgrave,
Schwartz and Berwick.

    Research areas

  • BOLD fMRI, Cerebral hemodynamics, Cerebral metabolic rate of oxygen, Cortical temperature, Hypercapnia, Seizures, Sensory stimulation

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