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.

Independent component analysis reveals dynamic ictal BOLD responses in EEG-fMRI data from focal epilepsy patients

“…On the other hand, restricting the HRF to the canonical shape, such as in the standard GLM method, may prevent the detection of real activations. For example, various studies have observed HRFs with late peaks (Bagshaw et al, 2004;Jacobs et al, 2008) or even early HRFs preceding the observed EEG events (Hawco et al, 2007;Jacobs et al, 2009;Moeller et al, 2008). Simulations have shown that HRFs delayed by only a few seconds may be undetected by the GLM (LeVan and ).…”

“…The 6 motion parameters (3 translations and 3 rotations) were also incorporated as confounds, since residual motion artifacts may contaminate the fMRI images even after motion correction (Friston et al, 1996). The BOLD changes related to the seizures were modeled as boxcar functions based on the timing and duration of the marked events, and convolved with four HRFs peaking at 3, 5, 7, and 9 s (Bagshaw et al, 2004). If the scanning session included interictal events, additional regressors were formed in the same way and treated as confounds in the model.…”

“…However, the HRF was not constrained to any particular shape, but was rather modeled by a windowed Fourier basis set spanning an interval from 10 s before to 20 s after the marked events. HRFs have been observed peaking as early as 3 s before or as late as 9 s after EEG events (Bagshaw et al, 2004;Moeller et al, 2008), so the selected time interval allows for a reasonable margin around the HRF peak. In the case of the canonical HRF, the onset is 5.4 s before the peak, and an undershoot occurs 5.4 s after the peak before resolving to baseline (Glover, 1999).…”

Variability of the hemodynamic response as a function of age and frequency of epileptic discharge in children with epilepsy

“…There is evidence that the actual HRF varies depending on the brain region, individual and time of the recording (Aguirre et al, 1998). The use of multiple HRFs (Bagshaw et al, 2004) and patient-specific HRFs (Kang et al, 2003) in EEG-fMRI indeed is more sensitive to detect positive and negative BOLD responses that would be otherwise missed with the standard model. We improved the sensitivity of EEG-fMRI with the use of four different HRFs (peaking at 3, 5, 7 and 9 s) in a group of children with symptomatic epilepsy (Jacobs et al, 2006), and as in adults, the responses seem to be specific, as demonstrated by their concordance with the anatomical areas related to the generation of the spikes, as well as with the potentially epileptogenic lesion/region.…”

Hemodynamic changes during posterior epilepsies: An EEG-fNIRS study

“…Considering a probable small lag between real onset and time to declare for patients who reported auras without surface EEG correlate, several GLM analyses were performed after moving the onsets backward in time (Bagshaw et al, 2004), relative to the fNIRS signals, by multiples of 4 s.…”