FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Physiological Basis of fMRI(and Neuroanatomy, in brief)

FMRI Undergraduate Course (PSY 181F) FMRI Graduate Course (NBIO 381, PSY

362)

Dr. Scott Huettel, Course Director

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

I.Neurophysiology

What brain processes consume energy?

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

There are two primary types of information flow in the CNS:

1) Signaling via action potentials (axonal activity) and

2) Integration via dendritic activity

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Action potential

Depolarization opens CA2+ channels

Vesicles fuse with presynaptic membrane

Neurotransmitter release

Neurotransmitters open ion channels on postsynaptic membrane

Change in potential

IPSP or EPSP

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Energy Demands of Integration/Signaling

Following activity, neurons require energy to restore concentration gradients of key

ions.Sodium-Potassium

pump takes sodium out of the cell while

bringing potassium into the cell.

Note that for action potentials, the

movement of ions is along gradients.

Key concept: activity of neurons does not itself require energy; restoring membrane potentials afterward does.

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

What metabolites are the sources of that energy?

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Oxygen (via

hemoglobin)

Glucose

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Facts about energy supply to brain

• 30-50 μmol/g/min of ATP for awake brain

• 10 μmol/g/min of ATP for comatose brain

• Information processing accounts for >75% of ATP consumption

• 54mL/min of blood for each 100 g of brain tissue

• Brain is ~3% of body weight, but demands 15-20% of blood flow and ~20% of blood oxygen

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Data from rodent models (Attwell & Laughlin, 2001). In humans, integrative activity

may be 50% greater.

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Why do neuroenergetics matter?

• Information reduction necessitated by energy demands!

• How could we increase information transmission?– Decrease membrane resistance

finer-resolution of dendritic activity (~200Hz)

– Increase action potential rate (~100-300Hz)

• Decreasing membrane resistance would increase maintenance costs

• Increasing action potential rate would rapidly increase signaling costs

• The energy available to the brain limits neural information processing

Attwell and Gibb, 2005

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

How are energy sources (metabolites) delivered?

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

The brain does not store glucose and oxygen in appreciable

quantities.

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Duvernoy, H. M., Delon, S., & Vannson, J. L.

(1981). Cortical blood vessels of the human brain. Brain Research

Bulletin, 7(5), 519-579.

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Arteries (1-25mm)Arterioles (10 - 300 microns)

precapillary sphinctersCapillaries (5-10 microns)Venules (8-50 microns)

Veins

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Key concepts in vascular system

• Vast change in scale from largest arteries to capillaries– Small changes in diameter result in large changes in

flow (2x diameter = 16x flow)

• Pulsatile flow in arteries smoothed out by resistance vessels (arterioles)

• Surface area of capillaries is essential for O2 exchange– Neurons are usually within 20μm from a capillary

• Capillaries are not always perfused!– Blood can bypass capillaries – Saves weight, cost (in blood), etc.

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

(anastomosis of internal carotids and basilar

artery)

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

ACA – Medial cortex

MCA – Anterolateral cortex

PCA – Posterior temporal and occipital lobes

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Sinus. n. An separation of the dura mater in

which blood drains into the venous system.

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Distribution of vascularization across cortical layers

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Capillary structure

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

How does function map onto blood flow?

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Iadecola, Nature Reviews Neuroscience, 2004

“[Mosso] relates of his female subject that one day whilst tracing her brain-pulse he observed a sudden rise with no apparent

outer or inner cause. She however confessed to him afterwards that at that

moment she had caught sight of a skull on top of a piece of furniture in the room, and

that this had given her a slight emotion.”

-James Principles… (1890)

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

“These facts seem to us to indicate the existence of an automatic mechanism by which the blood supply of any part of the cerebral tissue is varied in accordance with the activity of the chemical changes which underlie the functional action of that part.

Bearing in mind that strong evidence exists of localisation of function in the brain, we are of opinion that an automatic mechanism, of the kind just referred to, is well fitted to provide for a local variation of the blood supply in accordance with local variations of the functional activity.”

[Roy and Sherrington, 1890, emphasis added]

“Blood very likely may rush to each region of the cortex according as it is most active, but of this we know nothing.”

[James, 1890]

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Facts about blood flow

• Aorta peak flow: 90 cm/s• Internal carotid flow: ~ 40 cm/s• Smaller arteries: ~10-250 mm/s• Capillaries: ~ 1 mm/s• Venules and small veins: ~10-250

mm/s

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Stimulation of the sciatic nerve (in a rat) results in

arteriole dilation in somatosensory cortex.

There is a parallel change in blood velocity .

But, blood pressure remains relatively constant.

(This is a good thing.)

Adapted from Ngai et al., 1988

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Change in diameter of arterioles following sciatic (hindlimb) stimulation

Adapted from Ngai et al., 1988

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Change in arteriole dilation as a function of distance from active neurons

Iadecola, Nature Reviews Neuroscience, 2004

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

What triggers changes in blood flow?

• K+ : after synaptic activity• Adenosine : follows metabolic activity• Nitric oxide : released by active

neurons– Causes smooth muscles surrounding

arterioles to relax– NO inhibitors attenuate CBF, BOLD

• Neuronal activity ?

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Iadecola, Nature Reviews Neuroscience, 2004

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

How does the vascular system respond to neuronal activity?

Iadecola, Nature Reviews Neuroscience, 2004

Physiological data suggests that blood flow

changes may be associated with

preponderance of dendritic activity, but

disconnections are possible.

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Krimer, Muly, Williams, Goldman-Rakic, Nature Neuroscience, 1998

Pial Arteries (i.e., larger vessels) 10 m

Dopamine

Direct neuronal influences?

2 m

2 m

400 nm

400 nmNoradrenergic

On small capillaries, there are terminals of dopamine neurons. These appear to have slower influences than necessary for fMRI.

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Challenges to Neurogenic Control

• Slow time scale: DA effects = minutes

• DA receptor blockade does not modulate CBF increases w/activation (e.g., Esaki et al., 2002)

• Lack of spatial specificity of blood flow responses

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Summary of Physiology

• Information processing requires (substantial) energy– Energy is needed for restoring membrane

potentials

• Energy comes from Oxygen and Glucose– Minimal local availability

• Metabolites supplied by vascular system• Changes in blood flow with activity

– Changes may be disproportionate

• Next week: Can we identify some aspect of this process that is measurable using MRI?

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

II. Neuroanatomy

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Terminology: Planes of Section

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Terminology: Labels

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Brain in skull

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Brain covered with dura mater

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Gyri (bumps)

Sulci (valleys)

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

cerebellum

corpus callosum

spinal cord

pons

sinus

frontal lobeoccipital lobe

thalamus

skull

falx

medulla

midbrain

hypothalamus

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

A midsagittal MRI of the human head

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

frontal lobe

precentral gyrus

central sulcusparietal lobesuperior parietal

lobule

parieto-occipitalsulcus

occipital lobe

cerebellum

temporal lobe

Sylvian fissure

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

frontal lobe

occipital lobe

Parahippocampal gyrus

fusiform gyrus

inferiortemporal

gyrus

brain stem

Optic chiasma

substantia nigra

olfactory nerves

circle ofWillis

spinal cord

basilar artery

vertebral arteries

Fig 2.15

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

posterior corpus callosum

anterior corpus callosum

ventricle

caudate

thalamus

frontal lobe

occipital lobe

Fig 2.17

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Corpus Callosum

Internal Capsule

Caudate

Putamen

Globus PallidusAnterior

Commissure

(Collectively, these are known

as the basal ganglia)

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Insula

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Corpus Callosum and Indusium Griseum

FMRI – Week 5 – MR Signal Scott Huettel, Duke University

FMRI – Week 5 – MR Signal Scott Huettel, Duke University