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J Neurosci. 2004 Apr 14;24(15):3850-61.

Functional signal- and paradigm-dependent linear relationships between synaptic activity and hemodynamic responses in rat somatosensory cortex.

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Laboratory of Neuroimaging, Department of Neurology, University of California, Los Angeles, School of Medicine, Los Angeles, California 90024, USA.


Linear relationships between synaptic activity and hemodynamic responses are critically dependent on functional signal etiology and paradigm. To investigate these relationships, we simultaneously measured local field potentials (FPs) and optical intrinsic signals in rat somatosensory cortex while delivering a small number of electrical pulses to the hindpaw with varied stimulus intensity, number, and interstimulus interval. We used 570 and 610 nm optical signals to estimate cerebral blood volume (CBV) and oxygenation, respectively. The spatiotemporal evolution patterns and trial-by-trial correlation analyses revealed that CBV-related optical signals have higher fidelity to summed evoked FPs (SigmaFPs) than oxygenation-derived signals. CBV-related signals even correlated with minute SigmaFP fluctuations within trials of the same stimulus condition. Furthermore, hemodynamic signals (CBV and late oxygenation signals) increased linearly with SigmaFP while varying stimulus number, but they exhibited a threshold and steeper gradient while varying stimulus intensity, suggesting insufficiency of the homogeneity property of linear systems and the importance of spatiotemporal coherence of neuronal population activity in hemodynamic response formation. These stimulus paradigm-dependent linear and nonlinear relationships demonstrate that simple subtraction-based analyses of hemodynamic signals produced by complex stimulus paradigms may not reflect a difference in SigmaFPs between paradigms. Functional signal- and paradigm-dependent linearity have potentially profound implications for the interpretation of perfusion-based functional signals.

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