Context sensitivity of activity-dependent increases in cerebral blood flow

Abstract

Functional neuroimaging in humans is used widely to study brain function in relation to human disease and cognition. The neural basis of neuroimaging signals is probably synaptic activity, but the effect of context, defined as the interaction between synaptic inhibition, excitation, and the electroresponsive properties of the targeted neurons, is not well understood. We examined here the effect of interaction of synaptic excitation and net inhibition on the relationship between electrical activity and vascular signals in the cerebellar cortex. We show that stimulation of the net inhibitory parallel fibers simultaneously with stimulation of the excitatory climbing fibers leads to a further rise in total local field potentials (LFP) and cerebral blood flow (CBF) amplitudes, not a decrease, as predicted from theoretical studies. However, the combined stimulation of the parallel and climbing fiber systems produced changes in CBF and LFP that were smaller than their algebraic sum evoked by separate stimulation of either system. This finding was independent of the starting condition, i.e., whether inhibition was superimposed on a state of excitation or vice versa. The attenuation of the increases in LFP and CBF amplitudes was similar, suggesting that synaptic activity and CBF were coupled under these conditions. The result might be explained by a relative neuronal refractoriness that relates to the intrinsic membrane properties of Purkinje cells, which determine the recovery time of these cells. Our work implies that neuronal and vascular signals are context-sensitive and that their amplitudes are modulated by the electroresponsive properties of the targeted neurons.

Fusing EEG and fMRI based on a bottom-up model: inferring activation and effective connectivity in neural masses

“…The activation seen in functional imaging studies probably results from excitation rather than inhibition (Waldvogel et al 2000), while EEG reflects a competitive balance between them. Some authors, though, have asserted that neuronal inhibitions can raise fMRI and PET measures under certain extreme conditions (Tagamets & Horwitz 2001;Caesar et al 2003). In this issue, Horwitz et al (2005) evaluated the effect on PET and fMRI of using a large-scale excitatory and inhibitory computational model applied to a delayed matched-tosample task.…”

Integrated MEG/fMRI Model Validated Using Real Auditory Data

“…In addition, we considered the same rule for both EPSPs and IPSPs to calculate the synaptic activity. This assumption was based on experimental studies (Caesar et al 2003). Finally, we concluded that the synaptic activity was linearly related to N(t) (see Eqs.…”

Functional connectivity in fMRI: A modeling approach for estimation and for relating to local circuits

“…The effect of afferent neuronal context has recently been supported by electrophysiological experiments in the rat cerebellum (Caesar et al, 2003), where it was shown that simultaneously converging excitatory and inhibitory inputs to a region result in a smaller change in local blood flow than would be expected if they were purely additive. Our own modeling results also suggest that how such simultaneous inputs are reflected in regional metabolsim depends on the amount of local excitatory recurrence in the region .…”

“…Furthermore, methods such as structural equation modeling (SEM (McIntosh & Gonzalez-Lima, 1992;McIntosh & Gonzalez-Lima, 1994) and dynamic causal modeling (DCM; do not take synaptic inhibition and energetic consequences of modulatory neurotransmitter effects into account. For example, how synaptic inhibition affects local blood flow (fMRI signal) is not well understood (Jueptner & Weiller, 1995;Magistretti & Pellerin, 1999;Logothetis et al, 2001;Caesar et al, 2003). Because of this, a positive connection weight can not necessarily be interpreted as an excitatory underlying connection.…”