How does blood flow inform us about brain function?PowerPoint PresentationSlide 3Regionally specific, local brain “activation”Slide 5Visual processing and occipital activationInformation is transmitted between neurons via the synapseNeurons convey information via the action potentialCell-to-cell communication: Action potential, neurotransmitter, post-synaptic potentialSignaling to and from neuronsPost-synaptic activity (EPSP/IPSP)Input to dendrites/soma, integration, output via axonCerebral cortex: input to dendrites/soma, integration, output via axonsSimultaneous fMRI and electrophysiologySimultaneous fMRI/ephysBOLD signal and increased spike frequencyExtracellular field potentials are composed of both fast activity (MUA) and slow activity (LFP)BOLD correlates best with LFP (input)Excitatory and inhibitory circuitsBlood flow and input vs outputCBF correlates with summed input (sum of LFP)CBF correlates with input (LFP), but does not reveal nature of output (+/-)Slide 23How and why does CBF follow neuronal activity?The route of blood flow to the occipital cortexArterial supply: local change in CBF reflects change at arteriolar levelCortical neural structureCortical capillary vasculatureLocal vasodilation of arterioles accounts for change in rCBFVasodilation is spatially selectiveArteriolar dilation is greatest near neural activity, but also present en routeSlide 32dHb and T2* signalOxyHb overshootSlide 35Slide 36Blood flow and the organ of thoughtFrom neural activity to MR signalGlucose + oxygen = energyAstrocyte-neuron-lactate shuttleBrain blood flow and metabolismActivation-Related Energy ExpenditureSlide 43CBF, CBV, BOLDVariability in BOLD signalUtility of signal averagingHemodynamic response functionSlide 48Deactivations in neuroimagingActivation vs deactivationMechanisms of deactivationThe ‘default mode’ of brain functionSlide 53How does blood flow inform us about brain function?Cerebrovascular anatomy & neural regulation of CNS blood flowNeurovascular couplingHST 583Brad Dickerson, [email protected] specific, local brain “activation”Adapted from M. Raichle•Imaging signals reflect input and integrative activity within ensembles of neurons•Local blood flow changes reflect local changes in neuronal activity •Blood flow increases more than oxygen consumption•Activations reflect increased energy requirements, but are relatively small compared to overall metabolism of the brain•Blood flow change is relatively slow•DeactivationsReview: Raichle M & Minton M, Ann Rev Neurosci 2006Regionally specific, local brain “activation”•Imaging signals reflect input and integrative activity within ensembles of neurons•Local blood flow changes reflect local changes in neuronal activity •Blood flow increases more than oxygen consumption•Activations reflect increased energy requirements, but are relatively small compared to overall metabolism of the brain•Blood flow change is relatively slow•DeactivationsBlood Flow++PETfMRIBOLDVisual processing and occipital activationAdapted from M. RaichleInformation is transmitted between neurons via the synapseNeurons convey information via the action potentialCell-to-cell communication: Action potential, neurotransmitter, post-synaptic potentialEfferent signaling (output)Neuronal cell body (soma)->Action potential->axon->synapse (glutamate / GABA)Afferent signaling (input)Dendrite->EPSP (Glutamate) / IPSP (GABA)Integrative dendro-somatic activity->inhibitory/excitatory predominance->neuronal silence or firingSignaling to and from neuronsPost-synaptic activity (EPSP/IPSP)Input to dendrites/soma, integration, output via axonEach neuron integrates signals from a large number of inputsCerebral cortex: input to dendrites/soma, integration, output via axonsSimultaneous fMRI and electrophysiologyLogothetis N, Ann Rev Phys 2004Simultaneous fMRI/ephysLogothetis N, Ann Rev Phys 2004BOLD signal and increased spike frequencyExtracellular field potentials are composed of both fast activity (MUA) and slow activity (LFP)Action potentials are fast; 1/2-1 ms: represented by multi-unit activity (MUA)PSPs are slow: 2-100ms; represented by local field potentials (LFP)BOLD correlates best with LFP (input)Logothetis N, J Nsci 2003Excitatory and inhibitory circuitsBlood flow and input vs outputMathiesen C, J Phys 1998Purkinje cells: outputClimbing fibers: excitatory input to PurksParallel fibers: inhibitory input to PurksCBF correlates with summed input (sum of LFP)Mathiesen C, J Phys 1998CBF correlates with input (LFP), but does not reveal nature of output (+/-)Mathiesen C, J Phys 1998GABA antagonist disinhibits Purks; CBF increasesParallel fibers inhibit Purks; CBF increasesRegionally specific, local brain “activation”•Imaging signals reflect input and integrative activity within ensembles of neurons•Local blood flow changes reflect local changes in neuronal activity •Blood flow increases more than oxygen consumption•Activations reflect increased energy requirements, but are relatively small compared to overall metabolism of the brain•Blood flow change is relatively slow•DeactivationsBlood FlowOxygenUtilizationOxygenAvailability++PETfMRIBOLDHow and why does CBF follow neuronal activity?The route of blood flow to the occipital cortexArterial supply: local change in CBF reflects change at arteriolar level5 mmCortical neural structure5 mmCortical capillary vasculatureLayer IV:I ratiosCapillary 3.3:1; synapse 2.43:1Astrocyte 1.2:1; neuron 78.8:1Logothetis N, Ann Rev Phys 2004Local vasodilation of arterioles accounts for change in rCBFIn rat, recording at sensory cortex during sciatic nerve stimulationVasodilation is spatially selectiveA1/A2 supply hindlimb area; B nearby; C/D supply forelimbArteriolar dilation is greatest near neural activity, but also present en routeRegionally specific, local brain “activation”•Imaging signals reflect input and integrative activity within ensembles of neurons•Local blood flow changes reflect local changes in neuronal activity •Blood flow increases more than oxygen consumption•Activations reflect increased energy requirements, but are relatively small compared to overall metabolism of the brain•Blood flow change is relatively slow•DeactivationsdHb and T2* signalS Ogawa, 1990; see M Raichle, PNAS 1998 for historyOxyHb overshootOxyHb overshootRegionally specific, local brain “activation”•Imaging signals reflect input and integrative activity within