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<p>Neuromodulatory transmitters have vasoactive properties. Therefore, the impulse response function (IRF) linking spontaneous neuronal activity with hemodynamics may depend on neuromodulation. To test this hypothesis, we used optical imaging to measure norepinephrine (NE) or acetylcholine (ACh), calcium (Ca<sup>2+</sup>) activity of cortical neurons and hemodynamics in cerebral cortex in awake mice. We show that modeling of hemodynamics as a weighted sum of Ca<sup>2</sup><sup>+</sup>-specific and NE-specific IRFs (IRF<sub>Ca2+</sub> and IRF<sub>NE</sub>) convolved with the respective time courses dramatically improved the model performance compared to using IRF<sub>Ca2+</sub> alone. In contrast to NE, ACh was largely redundant with Ca<sup>2+</sup> and, therefore, did not improve the hemodynamic estimation. Because NE covaried with arousal, we observed instances of the diminished hemodynamic coherence between cortical regions during high arousal despite coherent behavior of the underlying neuronal Ca<sup>2+</sup> activity. We conclude that, without accounting for noradrenergic neuromodulation, diminished hemodynamic coherence can be falsely interpreted as neuronal desynchronizations in neuroimaging studies.</p>

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The neurovascular impulse response function differentially reflects intrinsic neuromodulation across cortical regions

  • 期刊论文

  • 发表日期：

    2026年3月26日

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  • Bradley C. Rauscher,
  • Natalie Fomin-Thunemann,
  • Sreekanth Kura,
  • Patrick R. Doran,
  • Pablo D. Perez,
  • Kıvılcım Kılıç,
  • Emily A. Martin,
  • Dora Balog,
  • Nathan X. Chai,
  • Francesca A. Froio,
  • Patrick F. Bloniasz,
  • Kate E. Herrema,
  • Rockwell P. Tang,
  • Scott G. Knudstrup,
  • Andrew Garcia,
  • John X. Jiang,
  • Jeffrey P. Gavornik,
  • Michael London,
  • David Kleinfeld,
  • Michael E. Hasselmo,
  • Laura D. Lewis,
  • Sava Sakadzic,
  • Lei Tian,
  • Gal Mishne,
  • Emily P. Stephen,
  • Martin Thunemann,
  • David A. Boas,
  • Anna Devor

摘要

Neuromodulatory transmitters have vasoactive properties. Therefore, the impulse response function (IRF) linking spontaneous neuronal activity with hemodynamics may depend on neuromodulation. To test this hypothesis, we used optical imaging to measure norepinephrine (NE) or acetylcholine (ACh), calcium (Ca2+) activity of cortical neurons and hemodynamics in cerebral cortex in awake mice. We show that modeling of hemodynamics as a weighted sum of Ca2+-specific and NE-specific IRFs (IRFCa2+ and IRFNE) convolved with the respective time courses dramatically improved the model performance compared to using IRFCa2+ alone. In contrast to NE, ACh was largely redundant with Ca2+ and, therefore, did not improve the hemodynamic estimation. Because NE covaried with arousal, we observed instances of the diminished hemodynamic coherence between cortical regions during high arousal despite coherent behavior of the underlying neuronal Ca2+ activity. We conclude that, without accounting for noradrenergic neuromodulation, diminished hemodynamic coherence can be falsely interpreted as neuronal desynchronizations in neuroimaging studies.