EEG-fMRI of focal epileptic spikes: analysis with multiple haemodynamic functions and comparison with gadolinium-enhanced MR angiograms

Abstract

Combined EEG-fMRI has recently been used to explore the BOLD responses to interictal epileptiform discharges. This study examines whether misspecification of the form of the haemodynamic response function (HRF) results in significant fMRI responses being missed in the statistical analysis. EEG-fMRI data from 31 patients with focal epilepsy were analysed with four HRFs peaking from 3 to 9 sec after each interictal event, in addition to a standard HRF that peaked after 5.4 sec. In four patients, fMRI responses were correlated with gadolinium-enhanced MR angiograms and with EEG data from intracranial electrodes. In an attempt to understand the absence of BOLD responses in a significant group of patients, the degree of signal loss occurring as a result of magnetic field inhomogeneities was compared with the detected fMRI responses in ten patients with temporal lobe spikes. Using multiple HRFs resulted in an increased percentage of data sets with significant fMRI activations, from 45% when using the standard HRF alone, to 62.5%. The standard HRF was good at detecting positive BOLD responses, but less appropriate for negative BOLD responses, the majority of which were more accurately modelled by an HRF that peaked later than the standard. Co-registration of statistical maps with gadolinium-enhanced MRIs suggested that the detected fMRI responses were not in general related to large veins. Signal loss in the temporal lobes seemed to be an important factor in 7 of 12 patients who did not show fMRI activations with any of the HRFs.

Figure 1

The five HRFs used in the analysis. P3 to P9 are single gamma functions with the same width as the standard (Glover) HRF.

Figure 2

Examples of the functional data in each signal loss category. A single transverse slice is shown, with the functional MRI data superimposed on the anatomical scan.

Figure 3

Examples of differences in fMRI responses between the standard and the optimum HRF analyses. A,C,E: The standard analysis for a particular fMRI response. B,D,F: The optimum analysis for a particular fMRI response. Standard (A) and P9 (B) analysis of data set 14. Standard (C) and P7 (D) analysis of data set 6 (activation). Standard (E) and P9 (F) analysis of data set 6 (deactivation). Increases in the volume and maximum t statistic can be observed.

Figure 4

The HRF model for which the t value and volume were maximum is plotted for all data sets that had a clearly superior value with one particular HRF (see Table I). Deactivations show a tendency to peak later than activations.

Figure 5

Comparison of standard and optimum analyses of two scans in the same patient (data sets 1 and 19). Standard (A) and P5 (B) analysis of data set 1. Standard (C) and P9 (D) analysis of data set 19. Similar regions are activated in the two sessions, but with different HRFs.

Figure 6

A: activation in the region of the supplementary motor area from data set 8 (patient B) overlaid on the gadolinium enhanced MRI. The statistical map was generated using P3. B: A cingulate gyrus activation in the same session, same patient, also with P3. C: A deactivation using P7. D: Another deactivation using P7. The ellipses in the left panels show the approximate extent of the fMRI response on the gadolinium‐enhanced MRI. Parts of the regions shown in A and B are close to large veins, but are consistent with SEEG data. The deactivation shown in C is close to the epileptogenic region defined by the scalp EEG and SEEG and is not close to any veins, while that in D is not consistent with the epileptogenic region and is close to the sagittal sinus.

Figure 7

A: Deactivation in the right temporal region from scan 9 in patient C overlaid on the gadolinium enhanced MRI. B: A left temporal deactivation in the same session, same patient. Both statistical maps were generated using P7. The ellipses in the left‐side images in A and B show the approximate extent of the fMRI response on the gadolinium enhanced MRI. Both regions are consistent with the epileptogenic zone defined by the scalp EEG and SEEG. The deactivation shown in B is within 5 mm of a large vein, but is considerably larger than it.