Sie sind auf Seite 1von 20

Imaging of neurovascular coupling in human

Habib Benali, PhD Laboratoire dImagerie Fonctionnelle, UMR-S 678 INSERM-UPMC Habib.Benali@imed.jussieu.fr

Neuron-astrocyte-hemodynamic model

Aubert & Costalat, Model of astrocyte-neuron interaction, JCBF&Metabolism, 25, 2005

Stimulus-hemodynamic model
Biophysical model
fin (t)

flux

Neuron-astrocyte stimulus u(t) = Stimulus

capillary

O2c

dHb, Vv

venous ballon

fout

Hemodynamic Response Function

Neuronastrocyte = stimulus
Linear model

O
2c

t t signal BOLD signal at voxel i

Stimulus (Neuronal response function)


Hemodynamic response function

Biophysical model : "balloon model"


Model (Buxton, 1998, Friston, 2000)

Neuronastrocyte = stimulus
O2c

d 2fin df in 1 = eu - 1 f 2 t s dt t f in dt
dv = 1 (f - va ) dt t0 in
1 dq = 1 (1 - (1 - E0) ) - a q ( fin v ) dt t0 v E0 1 fin 1

Biophysical model : "balloon model"


Neurovascular parameters in a rat model of healthy aging
young (Y, 45 months), old (O, 2432 months) and veryold (VO, 4041 months) male and female LOU/c rats were studied.

Model (Buxton,
1998, Friston, 2000)

Neuronastrocyte = stimulus
O2c

Dubeau S. et al. Neuroimage (2011)

LFP versus fMRI

LFP and BOLD of the visual cortex (3 and 6 seconds of stimulus). Bleu : activit LFP ; Rouge : BOLD; Gris : LFP convolu avec HRF Blue: LFP activity; red: BOLD; grey: LFP convolved with HRF
(Logothetis et al., 2001)

EEG power spectrum versus fMRI


Wan, et al., 2006. The neural basis of the hemodynamic response nonlinearity in human primary visual cortex: Implications for neurovascular coupling mechanism. NeuroImage 320 (3), 616625. EEG power spectrum ([1, 40] Hz) HRF Goense, J.B., Logothetis, N.K., 2008. Neurophysiology of the BOLD fMRI signal in awake monkeys. Curr. Biol. 18, 631640. EEG power spectrum ([1, 7]Hz, alpha [8, 15]Hz, beta [13, 30]Hz, gamma [30, 40]Hz) HRF Kilner, J., et al., 2005. Hemodynamic correlates of EEG: a heuristic. NeuroImage 28, 280286. Weighted EEG power spectrum HRF

EEG power spectrum versus fMRI

Envelop of Hilbert transform of the EEG power spectrum

HRF

BOLD Signal (fMRI)

Power spectrum h

BOLD

Which perspectives ?

Astrocytes activity and BOLD signal

J. Schummers, et al. Tuned Responses of Astrocytes and their Influence on hemodynamic signals in the visual cortex. Science 2008

Neuron-astrocyte-hemodynamic model

Aubert & Costalat, Model of astrocyte-neuron interaction, JCBF&Metabolism, 25, 2005

CBF activation PSP vs FR


Controlling the afferante connections Exc. and Inh. (Cells(unit of Purkinje), we observed an increase of CBF correlated to the sum of synaptic activity and not postsynaptic activity (Mathiesen et al. 1998, J Physiol 512, 555)

Local neural integrative process can drive the CBF increase irrespective of whether they generate action potentials (Iadecola et al. Nat Rev Neurosc 2004)

Close correlation between hemodynamic responses and neuronal synchronization power of LFP oscillations in the gamma range

Adapted from (Iadecola et al. Nat Rev Neurosc. 2004)

Conclusion : variation of postsynaptic potentential activity (PSP) CBF

CBF activity lack of energy


The available evidence indicates that the haemodynamic response to neural activity is not initiated by signals arising from the energy deficit of the tissue but, rather, is driven locally by fast glutamate-mediated signalling processes (Cauli et al. Frontiers in Neuroenergetics, 2010; 2:9) CBF is NOT controlled by Glc lack (Powers) nor O2 lack (Mintun et al. Proc Natl Acad Sci USA. 2004;101:659664). CBF response must be regulated by factors other than oxidative metabolism and total energy demand. [] The increase in lactate production (i.e., non-oxidative metabolism) was found in later studies to be a modulator of CBF increase (Mintun et al. Proc Natl Acad Sci USA. 2004; 101:659664). The fMRI observations confirm that CBF response to neuronal activity is driven more by anaerobic glycolysis, rather than oxygen demand. (Raichle et al. Annu Rev Neurosci. 2006;29:449-76)

Conclusion : PSPs, astrocyte signal & vasoactive mediators are mediator of BOLD

CBF activation Excitation vs inhibition


Exogenous GABA, acting via GABAA receptors, dilates precapillary microvessels in hippocampus and neocortex, and that blockage of GABAA receptors produces a constriction (fergus and Lee Cereb Blood Flow Metab 17:9921003) In the cerebellar cortex, GABA is not involved in activation-induced increases in CBF (Mathiesen et al. 1998, J Physiol 512, 555) In forebrain slices, stimulation of cortical GABA interneurons with neurovascular projections produces changes in the diameter of local microvessels. (Cauli et al. Frontiers in Neuroenergetics, 2010; 2:9)

There is evidence that blood flow in a number of brain structures, including neocortex, cerebellum, and hippocampus, may be controlled directly by glutamate and GABA (Logothetis and Wandell. Annu. Rev. Physiol. 2004. 66:73569 ) Conclusion : Consider both (Glu and GABA), but in which proportions ?

CBF vasoactive mediators


Astrocytes trigger local vasodilation when activated by glutamate. (Porras et al. J. Neurosci. 24, 96699673)

The vascular signals are mainly produced by increases in intracellular calcium in neurons and possibly astrocytes, which activate important enzymes that produce vasodilators to generate increments in flow and the positive BOLD signal (Lauritzen. 2005, Nature Reviews Neuroscience 6, 77-85)

Among the vasoactive agents, there are substances which are also involved in the generation of the extracellular ionic currents (such as K+ and H+), neurotransmitters (such as acetylcholine, GABA, catecholamines and neuropeptides) (Deneux 2006 PhD thesis) Conclusion: GLU and GABA are indirect vasoactive mediators

CBF vasoactive mediators


General conclusion
(i) different neuronal or astroglial messengers, likely acting in sequence, mediate the hemodynamic changes,

(ii) some recruited neurons release messengers that directly alter blood vessel tone, (iii) others act by modulating neuronal and astroglial activity, and (iv) astrocytes act as neurotransmitters. intermediaries for both excitatory and inhibitory

Conclusion 1. CBF is related to PPS (direct) & Glu/GABA (indirect) 2. CBF is related to Glu/GABA (extracellular or astrocytes)

Neuron-astrocyte-hemodynamic model

Neuron-astrocytehemodynamic model

Blanchard et al. BIOMAG, 2012

Collaborateurs

Denis SCHWARTZ Stphane SOCKEEL

Arnaud MESSE

Fabrice WENDLING

Solenna BLANCHARD

Olivier DAVID

Aurlie GARNIER

Alexandre VIDAL

Jean-Pierre FRANCOISE