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Neuroimaging: from image to Inference

Chris Rorden– fMRI limitations: relative to other tools used to infer

brain function.– fMRI signal: tiny, slow, hidden in noise.– fMRI processing: a sample experiment.– fMRI anatomy: stereotaxic space.

– See also:– http://www.biac.duke.edu/education/courses/fall05/fmri/

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Modern neuroscience

Different tools exist for inferring brain function.

No single tool dominates, as each has limitations.

This course focuses on fMRI.

Temporal resolution

good (millisecond) poor (months)

good(neuron)

poor(whole brain)

scr

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fmri

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Single Cell Recording

Directly measure neural activity.Exquisite timing informationPrecise spatial informationOften, no statistics required!

•Each line is one trial.•Each stripe is neuron firing.•Note: firing increases whenever monkey reaches or watches reaching.

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Single Cell Recording

With SCR, we are very close to the data.We can clearly see big effects without

processing.Unfortunately, there are limitations:

– Invasive (needle in brain)Typically constrained to animals, so difficult to directly

infer human brain function.

– Limited field of view: just a few neurons at a time.

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fMRI Processing

Unlike SCR, we must heavily process fMRI data to extract a signal.

The signal in the raw fMRI data is influenced by many factors other than brain activity.

We need to filter the data to remove these artifacts.

We will examine why each of these steps is used.

Processing Steps1. Motion Correct

1. Spatial

2. Intensity

2. Physiological Noise Removal

3. Temporal Filtering

4. Temporal Slice Time Correct

5. Spatial Smoothing

6. Normalize

7. Statistics

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fMRI signal sluggish

Unlike SCR, huge delay between activity and signal change.

Visual cortex shows peak response ~5s after visual stimuli.

Indirect measure of brain activity

0 6 12 18 24

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1

0

Time (seconds)

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What is the fMRI signal

fMRI is ‘Blood Oxygenation Level Dependent’ measure (BOLD).

Brain regions become oxygen rich after activity. Very indirect measure.

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Lets conduct a study

Anatomical Hypothesis: lesion studies suggest location for motor-hand areas.

Ask person to tap finger while in MRI scanner – predict contralateral activity in motor hand area..

M1: movement

S1: sensation

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Task

Task has three conditions:1. Up arrows: do nothing

2. Left arrows: press left button each time arrow flashes.

3. Right arrows: press right button every time arrow flashes.

Block design: each condition repeats rapidly for 11.2 sec.

No sequential repeats: block of left arrows always followed by block of either up or right arrows.

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Data Collection

Participant Lies in scanner watching computer screen.

Taps left/right finger after seeing left/right arrows.

Collect 120 3D volumes of data, one every 3s (total time = 6min).

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Raw Data

The scanner reconstructs 120 3D volumes.– Each volume = 64x64x36

voxels– Each voxel is 3x3x3mm.

We need to process this raw data to detect task-related changes.

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Motion Correction

Unfortunately, people move their heads a little during scanning. We need to process the data to create motion-stabilized

images. Otherwise, we will not be looking at the same brain area over

time.

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Spatial smoothing

Each voxel is noisy By blurring the image, we can get a more stable signal

(neighbors show similar effects, noise spikes attenuated).

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Predicted fMRI signal

We need to generate a statistical model. We convolve expected brain activity with

hemodynamic response to get predicted signal.

Predicted fMRI signal

=

Neural Signal HRF

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Predicted fMRI signal

We generate predictions for neural responses for the left and right arrows across our dataset.

Statistics will identify which areas show this pattern of activity. Several possible statistical contrasts (crucial to inference):

1. Activity correlated with left arrows: visual cortex, bilateral motor.2. More activity for left than right arrows: contralateral motor.

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Voxelwise statistics

We compute the probability for every voxel in the brain.

We observe that right arrows precede activation in the left motor cortex and right cerebellum.

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fMRI signal change is tiny, noise is high

Right motor cortex becomes brighter following movement of left hand. Note signal increases from ~12950 to ~13100, only about 1.2% And this is after all of our complicated processing to reduce noise.

0 100 200 300

L_Tap right

12900

13000

13100

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Coordinates - normalization

Different people’s brains look different ‘Normalizing’ adjusts overall size and orientation

Raw Images Normalized Images

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Why normalize?

Stereotaxic coordinates analogous to longitude– Universal description for anatomical location– Allows other to replicate findings– Allows between-subject analysis: crucial for inference that

effects generalize across humanity.

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Goals for this course

fMRI is notoriously difficult technique– Sluggish signal– Poor signal/noise– Must find meaningful statistical contrasts

This seminar reveals how to– Devise meaningful contrasts– Maximize signal, minimize noise– Control for statistical errors.

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Safety

MRI uses very strong magnet and radiofrequencies– 3T= ~x60,000 field that aligns compass– Metal and electronic devices are not compatible.

MRI scanning makes loud sounds– Rapid gradient switching creates auditory noise.– Auditory protection crucial.

MRI scanning is confined– Claustrophobia is a concern.

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Summary of Lectures

1. Introduction2. Physics I: Hardware and Acquisition3. Physics II: Contrasts and Protocols4. fMRI Paradigm Design5. fMRI Statistics and Thresholding6. fMRI Spatial Processing7. fMRI Temporal Processing8. VBM & DTI: subtle structural changes9. Lesion Mapping: overt structural changes10. Advanced and Alternative Techniques

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Which tools

There are many tools available for analysis.

Different strengths.We predominantly focus

on SPM and FSL.These are both free,

popular and have good user support.

Tool SFN04

SPM 78.5%

AFNI 9.1%

FSL 7.4%

BrainVoyager 4.1%

https://cirl.berkeley.edu/view/Grants/BrainPyMotivation

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Reporting findings

How do we describe anatomy to others?

We could use anatomical names, but often hard to identify.

We could use Brodmann’s Areas, but this requires histology – not suitable for invivo research.

Both show large between-subject variability.

Requires anatomical coordinate system.

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Relative Coordinates

On the globe we talk about North, South, East and West.

Lets explore the coordinates for the brain.

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Orientation - animals

Cranialhead

Rostralbeak Caudal

tail

Dorsalback

Ventralbelly

Rostral Caudal

Ventral

Dorsal

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Coordinates – Dorsal Ventral

Human dorsal/ventral differ for brain and spine.– Head/Foot, Superior/Inferior, Anterior/Posterior not ambiguous.

DorsalVentral

Dorsal

Ventral

DorsalVentral

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Coordinates – Human

CR CR

C

R

Human rostral/caudal differ for brain and spine.– Head/Foot, Superior/Inferior, Anterior/Posterior not ambiguous.

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Orientation

Human anatomy described as if person is standing

If person is lying down, we would still say the head is superior to feet.

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Anatomy – Relative Directions

Posterior <> Anterior

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> A

nte

rior

Ven

tral

<>

Dor

sal

lateral < medial > lateral

Anterior/Posterioraka Rostral/Caudal

Ventral/Dorsalaka Inferior/Superioraka Foot/Head

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Coordinates - Anatomy

3 Common Views of Brain:– Coronal (head on)– Axial (bird’s eye), aka

Transverse. – Sagittal (profile)

sagittalcoronal

axial

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Coronal

Corona: a coronal plane is parallel to crown that passes from ear to ear

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Transverse

Transverse/Axial: perpendicular to the long axis

Example: cucumber slices are transverse to long axis.

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Sagittal

Sagittal – ‘arrow like’– Sagittal cut divides object into left

and right– sagittal suture looks like an arrow.

top view

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Sagittal and Midsagittal

A Sagittal slice down the midline is called the ‘midsagittal’ view.

midsagittal sagittal

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Oblique Slices

Slices that are not cut parallel to an orthogonal plane are called ‘oblique’.

The oblique blue slice is neither Coronal nor Axial.

Ax

Cor

Oblique