fMRI (functional Magnetic Resonance Imaging) and Optic Neuritis

1. 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

2. MRI vs. fMRI Functional MRI (fMRI) studies brain function. MRI studies brain anatomy. Source: Jody Culham’s fMRI for Dummies web site

3. fMRI Setup Source: Jody Culham’s fMRI for Dummies web site

4. Hemodynamic Response Function • % signal change • = (point – baseline)/baseline • usually 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 peak • signal peaks 4-6 sec after stimulus begins • post stimulus undershoot • signal suppressed after stimulation ends Source: Jody Culham’s fMRI for Dummies web site

5. MRI vs. fMRI MRI fMRI oneimage • fMRI • Blood Oxygenation Level Dependent (BOLD) signal • indirect measure of neural activity … many images (e.g., every 2 sec for 5 mins)  neural activity   blood oxygen   fMRI signal Source: Jody Culham’s fMRI for Dummies web site

6. 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

7. 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)

8. 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

9. 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) Acitvation Red 8hz photic stimulation to one eye 12 cycles of alteration 5 volumes per state Baseline

10. 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

11. fMRI data analysis: GBAM GBAM: 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

12. fMRI data analysis: GBAM Time series FPQ maps Median FPQ maps observed • 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 * randomized Subject 1 observed randomized Subject 2 *Model fitting and registration

13. Results Left: 3 selected slices for controls (A and B), unaffected patient 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

14. 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

15. 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

16. And…. Am Done… Qs?