Macrocircuit Imaging Ed Boyden Synthetic Neurobiology Laboratory - PowerPoint PPT Presentation

Macrocircuit Imaging Ed Boyden Synthetic Neurobiology Laboratory Massachusetts Institute of Technology Invited lecture at Stanford in CS379C on April 10, 2013

Today’s outline PRINCIPLES, USES, UNKNOWNS EEG MEG PET NIR fMRI

Brain scanning • What we will cover today – Physical principles of brain signals – Intuitions for how to think about brain signals • What we will not cover today – Advanced signal processing – Software/algorithms • Enough classes do this (i.e., half of Course 6) • Takes forever • Probably easier to read it and go through the math, than to hear a lecture

Brain scanning • Read directly from the brain itself – EEG – MEG • Watch something inside the brain emit – PET • Deliver energy and monitor changes induced by brain – NIR – fMRI

EEG • Electroencephalography – About as simple as it gets – Put electrode on scalp • Sometimes after abrading the surface • Gold + conductive gel • Silver/silver chloride – Capacitive sensing – non-contact sensors – Instrumentation amplifier to subtract out small voltages • Voltage levels: 100-900 µ V (lower with higher frequency) – Much lower than in the brain • Frequency band: 1-70 Hz – Much lower than in the brain

Simple to build • OpenEEG project

How many electrodes? • Often use 1-2 dozen sites

Uses • Rapid, effective, characterization of brain state – Simple, low-bitrate brain-computer interfaces – Art – Videogames • Few electrodes • Dry electrodes

RE: Altered oscillations as pathological signatures • Pathological states have • Spike-wave discharges specific alterations, e.g. (seconds long, 1-3 Hz epilepsy oscillation) • Paroxysmal fast (6-10 Hz) – Absence seizures oscillations – Tonic-clonic seizures

RE: Spatial structure of oscillations • Local sleep – Do a motor task à see enhanced slow waves after learning, in the motor area (Huber et al., 2004) • ‘Dolphins sleep with half their brain’

Visual evoked potentials • EEG: over occipital lobe, after a stimulus presentation – Easy to use to check for blindness Dipoles hypothesized to be V1 à V2 à parietal Also a propagating wave? Voltage-imaging studies ongoing.

Time+space: role of ongoing activity • State-dependence of sensory inputs – The ongoing phase of the EEG determines the impact of a sensory input, for example • Voltage-dye expt (Arieli et al., 1996) Averaged evoked (like a visual evoked potential) Initial Summed Actual – No behavioral work as to the significance of this, yet. But the EEG cycles could set detection thresholds, etc.

‘Whole brain’ connectivity • TMS + EEG: send out a test pulse, see where it goes – TMS of motor cortex, in waking and sleeping individuals wearing high-density EEG electrode arrays (Massimini et al., 2005)

Invasive EEG • Electrocorticogram – Remove the skull and dura, but still use surface electrodes – Can get higher frequencies (100- 500 Hz) than EEG – BCI – much higher bitrate (Leuthardt et al., 2004)

MEG • Magnetoencephalography – Ampere’s law: current causes a magnetic field – Direct pickup of brain’s magnetic field – The hard part: sensing the magnetic field • 10 -14 T or less! (Earth = 5 x 10 -5 T) • Early days used regular copper coil, but now everyone uses SQUIDs • Need high magnetic permeability shielded room (nickel-iron alloy (75% nickel, 15% iron, plus copper and molybdenum) )

MEG sensors • SQUIDs – Superconducting ring, interrupted by a thin insulator • I = current through the junction • φ = phase of electron wavefunctions across junction = 2 π Φ / Φ 0 • Ic = constant (critical current) • Φ = magnetic flux in ring, Φ 0 = flux quantum ( 2.07 × 10 − 15 T m 2 ) Ι = Ι c * sin( π Φ / Φ 0 )

Uses • Expensive, but in principle you can see deep magnetic sources, without distortion by overlying tissues – Magnetic fields pass through unaffected, unlike EEG – Decent spatial resolution – Very fast time resolution PROBLEM: Underconstrained inversion of the sensors into deep magnetic fields Lots of effort to invent assumptions that allow inversion of the sensors.

Brain scanning • Read directly from the brain itself – EEG – MEG • Watch something inside the brain emit – PET – SPECT • Deliver energy and monitor changes induced by brain – NIR – fMRI

Properties of the brain

Brain scanning • Read directly from the brain itself – EEG – MEG • Watch something inside the brain emit – PET – SPECT • Deliver energy and monitor changes induced by brain – NIR – fMRI

General principles • No need for magnetic fields like MRI (safe for implanted patients) • Functional: can measure glucose, dopamine binding, etc. • Energy transmits through tissue. Image indicates – Distribution of energy sources – Molecular environments or properties of tissue through which radiation propagates • Contrast = signal vs. background, Δ I/I • Signal-to-noise = signal vs. variation of signal • Resolution = Δ x • Often calibrate these using “standard” signals or materials – Current in a wire = “axon” – Water, blood, etc. = simulates flow in body

Tomography: building up a 3-D picture from lots of 2-D pictures • Take pictures from all sides of an object • For each 2-D picture, each point represents a line integral

Same holds in polar coordinates R

PET • Positron Emission Tomography – Radioactive isotope introduced into body • Isotope: different numbers of neutrons in the nucleus • Unstable: called a radionuclide – Not enough neutrons (usu 150% of # of protons) – Decays, emitting positron • weak force decay: p + à n 0 + β + + ν e • Half life (t 1/2 = ln(2) * τ , where decay is e -t/ τ ) – carbon-11 20.3 minutes – oxygen-15 2.03 minutes – fluorine-18 109.8 minutes ß About ideal! – bromine-75 98.0 minutes

PET • Positron Emission Tomography – Positron hits electron • β + + β − à γ + γ (0.511 MeV each) • mean free path of the positrons in brain tissue limits the resolution of PET scanning to about 4 mm • Conservation of energy, linear momentum, angular momentum • Gamma rays emitted in opposite directions, polarized in opposite directions

Detection of the gamma rays • Two gamma rays emitted in opposite directions, with opposite angular momentum – Hits scintillator (e.g., bismuth germanate, BGO), which emits light, which goes to PMT, which causes current – 0 th order: the pair of detectors • Over time: intersection point of these lines yields the target • Lines project back to sources – 1 st order: the time-of-flight • 1 ft = 1 ns, hard to do, but modern machines do it

18 FDG: 18 fluoro-deoxyglucose • Accumulated by metabolizing cells (esp if low blood sugar – often patients fast) • Can’t be metabolized until it decays (2 hr) • When decays, 18 F à 18 O, and becomes normal glucose (except with slightly higher molecular weight; extra neutron) • Need a cyclotron to make FDG – Must be within 2 hours of a cyclotron

Examples • PET of depression – 15 O water – blood flow measurement – (Mayberg et al., 2002)

Can use radionuclides attached to probes other than FDG • 11 C-raclopride – Binds to D2 receptor; antagonist – Easily displaced by dopamine • Less binding = more dopamine – Can see dopamine release when: • Taking nicotine • Changing a decision-making rule • Cocaine abusers taking Ritalin (Volkow et al., 1997) – Less dopamine release in abusers of cocaine; correlates with lower self-report of pleasure – More dopamine release when abusers see paraphernalia (e.g., pipes, etc.)

SPECT • Single photon emission computed tomography – 99m Tc-HMPAO (hexamethylpropylene amine oxime) • Blood contrast agent • 99m Tc: half-life of 6.01 hours, excited state of the nucleus (m = ‘metastable’) – Made from decay of 99 Mo à 99m Tc + β + ν (half-life, 66 hours; cheaper than 18 F) • Relaxes by releasing a gamma ray (140 keV), and nucleons rearrange

SPECT • Detecting the gamma ray: the gamma camera – Goes through collimator (sheets of lead) – Hits a detector crystal (sodium iodide), which scintillates (i.e., fluoresces) – Photons go through PMT, which amplifies signal via electron cascade – Electrons picked up and digitized • 1-3 gamma cameras circle the patient – As they rotate, record 2-D snapshots of gamma-ray intensity – Backproject to form 3-D image

SPECT Images of Common Neurological and Psychiatric Disorders Alzheimer’s Disease Right Sided Stroke pervasive hypoperfusion Depression Head Trauma to left PFC - severe increased limbic activity (left) and decreased aggression problems/violence prefrontal and temporal lobe activity http://brighamrad.harvard.edu/education/online/BrainSPECT/Main_Slide_Show/Main_SS.html

PET and SPECT vs. other methods • PET and SPECT measures absolute levels of blood flow • PET and SPECT can be used without large magnetic field (compatible with brain implants) • PET and SPECT can be used with functional indicators (e.g., dopamine binding, etc.)