fMRI (functional Magnetic Resonance Imaging)

and Optic Neuritis

Recovery from optic neuritis is associated with a change in the distribution of cerebral response to visual stimulation: a fMRI study

Functional magnetic resonance imaging of the cortical response to photic stimulation in humans following optic neuritis recovery

-A.J Thompson et al

MRI studies brain anatomy.Functional MRI (fMRI) studies brain function.

MRI vs. fMRI

Source: Jody Culham’s fMRI for Dummies web site

fMRI Setup

Source: Jody Culham’s fMRI for Dummies web site

% signal change = (point – baseline)/baselineusually 0.5-3%

initial dip-more focal and potentially a better measure-somewhat elusive so far, not everyone can find it

time to rise signal begins to rise soon after stimulus begins

time to peaksignal peaks 4-6 sec after stimulus begins

post stimulus undershootsignal suppressed after stimulation ends

Source: Jody Culham’s fMRI for Dummies web site

Hemodynamic Response Function

MRI vs. fMRI

neural activity blood oxygen fMRI signal

MRI fMRI

one image

many images (e.g., every 2 sec for 5 mins)

fMRI Blood Oxygenation Level Dependent (BOLD) signal

indirect measure of neural activity …

Source: Jody Culham’s fMRI for Dummies web site

The papers…

Both by the same authors and has similar experimental setups

The second paper is a follow up to the results presented in the first paper

Terms and Observations

Myelin: The fatty sheath coating the axons of the nerves; it allows efficient conduction of nerve impulses.

MS (Multiple Sclerosis): Demyelination of the CNS ON (Optic neuritis): An inflammatory disorder of the optic nerve that

usually occurs in only one eye and causes visual loss and sometimes blindness. It is generally temporary.

Temporary: Patients usually regain visual acuity after a period of time. Visual acuity: Sharpness or clearness of vision.

Measured using Snellen charts and Ishihara color plates.

Question: How is visual acuity regained? Given that ON is a common precursor to MS. (Implying that the optic pathways are probably irreparably damaged)

Hypothesis and Study

Possibility of cortical re-adaptation (functional reorganization)

Use fMRI to study patients who have recovered from ON.

Pick patients who had only one eye affected.

Match with equal number of normal subjects

Conduct additional structural scans and VEP (Visual Evoked Potential)

Interpret the fMRI analysis

fMRI experimental setup

1.5 T magnet One volume every 4 seconds, for a duration of 8 minutes (8*60/4 = 120) Each volume has a size 96*96*10 vox (2.5 mm in plane 5mm thick slices)

0 50 100 150 200 250 300 350 400 450 5000

0.5

1

1.5

2

Baseline

AcitvationRed 8hz photic stimulationto one eye 12 cycles of

alteration

5 volumes perstate

Preprocessing: Head motion correction Reference [9] of the first paper: Methods of Diagnosis and treatment

of stimulus-correlated motion in generic brain activation studies using fMRI

Find mean image of time series (base)

Minimize MAD (mean absolute difference) of each with respect to base

Realignment done using tricubic spline interpolation

Difference between SCM (Stimulus Correlated Motion) between the two groups was not significant. (Paper does not mention the actual values for them! ). Hence not accounted for in this study

fMRI data analysis: GBAMGBAM: Generic Brain Activation Map. Reference [13] :Generic brain activation mapping in functional magnetic resonance imaging: a non parametric approach.

Fit a model: Y(t) is the time course of a single

voxel (IMP: slice wise) w is fundamental frequency of

stimulus 2 harmonic components a+bt represents a linear trend rho(t) is the residual

rho(t) is usually a first order autoregressive process.

Pseudogeneralised lest squares fitting Reduce each time course to a single

value reflecting the power at fundamental frequency

fMRI data analysis: GBAM To check the hypothesis that a given

voxel FPQ value is determined by periodic experimental design, authors use Randomization testing Randomly permute the slices (of each

volume with corresponding slice location in another volume) of the time series to obtain 10 random time courses

Another paper asserts that the FPQ sampled this way is indistinguishable from a FPQ derived from image sequences when no stimulus is provided

Calculate the FPQ maps for each of these time courses

Generic analysis: Register these maps into the standard space (Talairach and Tournoux)

GBAM obtained by comparing medians

observed

randomized

Time series FPQ maps

observed

randomized

Subject 1

Subject 2

MedianFPQ maps

*Model fitting and registration

*

ResultsLeft: 3 selected slices for controls (A and B), unaffectedpatient eye (C) and ON affected patient eye (D)Bottom: Comparison of VEP delay in affected patient eye

Key observations: Extra occipital response and phase of this response

Results

The identified extra occipital areas are known to have extensive connections with the visual processing system

Unaffected eye also displayed extra cortical activation areas. Possibly due to clinically silent abnormality

During an episode of ON VEP amplitude decreases and latency increases. After recovery, amplitude more or less returns back to normal but latency persists

The result of reduced volume in the visual cortex correlates with previous studies

But did not report extra occipital response (due to methodological differences?)

Strengths the hypothesis of possible cortical reorganization

Results

Since the activation in the extra occipital areas was almost perfectly out of phase with stimulus, they conducted another study varying the epoch duration to rule out this chance happening

Reduced extent of response across groups to the longer stimulus duration. (Largest effect seen in affected eye)

Rules out a fixed delay in extra occipital activation and implies phase dependency

The difference in visual cortex activation volume was more significant with longer epoch

Possibly reasons: Active inhibition during baseline Redistribution of cortical blood supply (Stolen) Possible ‘after image’ in patients

And….

Am Done…

Qs?