How does blood flow inform us about brain function?

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How does blood flow inform us about brain
function?
Cerebrovascular anatomy neural regulation of
CNS blood flow Neurovascular coupling
HST 583 Brad Dickerson, M.D. bradd_at_nmr.mgh.harvard
.edu
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Regionally 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
• Deactivations

Adapted from M. Raichle
Review Raichle M Minton M, Ann Rev Neurosci
2006
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Regionally 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
• Deactivations

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Visual processing and occipital activation
fMRI
PET
BOLD
Adapted from M. Raichle
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Information is transmitted between neurons via
the synapse
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Neurons convey information via the action
potential
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Cell-to-cell communication Action potential,
neurotransmitter, post-synaptic potential
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Signaling to and from neurons
Efferent signaling (output) Neuronal cell body
(soma)-gtAction potential-gt axon-gtsynapse
(glutamate / GABA) Afferent signaling
(input) Dendrite-gtEPSP (Glutamate) / IPSP
(GABA) Integrative dendro-somatic
activity-gtinhibitory/excitatory
predominance-gtneuronal silence or firing
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Post-synaptic activity (EPSP/IPSP)
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Input to dendrites/soma, integration, output via
axon
Each neuron integrates signals from a large
number of inputs
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Cerebral cortex input to dendrites/soma,
integration, output via axons
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Simultaneous fMRI and electrophysiology
Logothetis N, Ann Rev Phys 2004
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Simultaneous fMRI/ephys
Logothetis N, Ann Rev Phys 2004
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BOLD signal and increased spike frequency
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Extracellular 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)
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BOLD correlates best with LFP (input)
Logothetis N, J Nsci 2003
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Excitatory and inhibitory circuits
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Blood flow and input vs output
Purkinje cells output Climbing fibers
excitatory input to Purks Parallel fibers
inhibitory input to Purks
Mathiesen C, J Phys 1998
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CBF correlates with summed input (sum of LFP)
Mathiesen C, J Phys 1998
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CBF correlates with input (LFP), but does not
reveal nature of output (/-)
Parallel fibers inhibit Purks CBF increases
GABA antagonist disinhibits Purks CBF increases
Mathiesen C, J Phys 1998
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Regionally 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
• Deactivations

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How and why does CBF follow neuronal activity?
fMRI
PET
BOLD
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The route of blood flow to the occipital cortex
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Arterial supply local change in CBF reflects
change at arteriolar level
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Cortical neural structure
5 mm
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Cortical capillary vasculature
Layer IVI ratios Capillary 3.31 synapse
2.431 Astrocyte 1.21 neuron 78.81
5 mm
Logothetis N, Ann Rev Phys 2004
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Local vasodilation of arterioles accounts for
change in rCBF
In rat, recording at sensory cortex during
sciatic nerve stimulation
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Vasodilation is spatially selective
A1/A2 supply hindlimb area B nearby C/D supply
forelimb
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Arteriolar dilation is greatest near neural
activity, but also present en route
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Regionally 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
• Deactivations

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dHb and T2 signal
S Ogawa, 1990 see M Raichle, PNAS 1998 for
history
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OxyHb overshoot
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OxyHb overshoot
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Regionally 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
• Deactivations

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Blood flow and the organ of thought

• The brain requires blood for
• General support of maintenance functions, like
  every organ - requires energy (ATP)
• Specific localized support of functional activity
  related to neural activity - requires energy
  (ATP)
• Blood supplies substrates for energy production
  Glucose and oxygen
• 750 ml/min

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From neural activity to MR signal
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Glucose oxygen energy
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Astrocyte-neuron-lactate shuttle
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Brain blood flow and metabolism
Slide courtesy of M. Raichle
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Activation-Related Energy Expenditure
Bottom Line Activations represent very small
incremental costs to the brain
M Raichle
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Regionally 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
• Deactivations

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CBF, CBV, BOLD
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Variability in BOLD signal
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Utility of signal averaging
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Hemodynamic response function
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Regionally 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
• Deactivations

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Deactivations in neuroimaging
Regions consistently shown to deactivate in
visual tasks (19 different studies)
Regions with highest resting metabolism
Gusnard DA, Nat Rev Nsci, 2001
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Activation vs deactivation
Deactivation not increased inhibitory activity,
maybe decreased tonic input?
Gusnard DA, Nat Rev Nsci, 2001
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Mechanisms of deactivation
Activation Task increase more than control, or
decrease less than control
Deactivation Task increase less than control, or
decrease more than control
Gusnard DA, Nat Rev Nsci, 2001
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The default mode of brain function
Dorsolateral parietal, medial parietal/precuneus,
medial prefrontal/orbitofrontal a sentinal
network?
Raichle ME, PNAS, 2001
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Are activations the whole story?
M Raichle