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-fig-06-02-0.jpg FMRI – Week 5 – MR Signal Scott Huettel, Duke University

There are two primary types of information flow in the CNS: Signaling via action potentials (axonal activity) and Integration via dendritic activity FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Depolarization opens CA2+ channels Action potential Depolarization opens CA2+ channels Vesicles fuse with presynaptic membrane Neurotransmitter release Neurotransmitters open ion channels on postsynaptic membrane fmri-fig-06-04-0.jpg 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. fmri-fig-06-03-0.jpg 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-fig-06-05-0.jpg 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) Data from rodent models (Attwell & Laughlin, 2001). In humans, integrative activity may be 50% greater. fmri-fig-06-06-0.jpg 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

fmri-fig-06-08-0.jpg 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 sphincters Capillaries (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-fig-06-10-1.jpg FMRI – Week 5 – MR Signal Scott Huettel, Duke University

(anastomosis of internal carotids and basilar artery) fmri-fig-06-10-2.jpg FMRI – Week 5 – MR Signal Scott Huettel, Duke University

MCA – Anterolateral cortex ACA – Medial cortex MCA – Anterolateral cortex PCA – Posterior temporal and occipital lobes fmri-fig-06-11-1.jpg 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-fig-06-11-3.jpg 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-fig-06-13-0.jpg FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Capillary structure fmri-fig-06-09-0.jpg 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) Iadecola, Nature Reviews Neuroscience, 2004 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

There is a parallel change in blood velocity . Stimulation of the sciatic nerve (in a rat) results in arteriole dilation in somatosensory cortex. There is a parallel change in blood velocity . fmri-fig-06-14-1.jpg 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 fmri-fig-06-15-0.jpg 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 fmri-fig-06-16-0.jpg 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? Physiological data suggests that blood flow changes may be associated with preponderance of dendritic activity, but disconnections are possible. Iadecola, Nature Reviews Neuroscience, 2004 FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Direct neuronal influences? 2 m 400 nm On small capillaries, there are terminals of dopamine neurons. These appear to have slower influences than necessary for fMRI. Noradrenergic Dopamine Pial Arteries (i.e., larger vessels) 10 m Krimer, Muly, Williams, Goldman-Rakic, Nature Neuroscience, 1998 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

corpus callosum falx skull hypothalamus occipital lobe frontal lobe sinus thalamus midbrain pons cerebellum medulla spinal cord FMRI – Week 5 – MR Signal Scott Huettel, Duke University

A midsagittal MRI of the human head fmri-fig-06-19-0.jpg FMRI – Week 5 – MR Signal Scott Huettel, Duke University

parietal lobe central sulcus superior parietal lobule precentral gyrus parieto-occipital sulcus occipital lobe frontal lobe Sylvian fissure cerebellum temporal lobe FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Fig 2.15 frontal lobe olfactory nerves Optic chiasma Parahippocampal gyrus circle of Willis fusiform gyrus inferior temporal gyrus basilar artery brain stem substantia nigra vertebral arteries spinal cord occipital lobe Fig 2.15 FMRI – Week 5 – MR Signal Scott Huettel, Duke University

Fig 2.17 frontal lobe anterior corpus callosum caudate ventricle thalamus posterior corpus callosum occipital lobe Fig 2.17 FMRI – Week 5 – MR Signal Scott Huettel, Duke University

(Collectively, these are known as the basal ganglia) Caudate Corpus Callosum Putamen Internal Capsule Globus Pallidus Anterior 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-fig-06-21-0.jpg FMRI – Week 5 – MR Signal Scott Huettel, Duke University

fmri-fig-06-22-1.jpg FMRI – Week 5 – MR Signal Scott Huettel, Duke University