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EARLY DEVELOPMENT OF THE EEG-FMRI TECHNIQUE
In 1992 John Ives, Steve Warach and Franz
Schmitt first performed an electroencephalogram (EEG) into a 1.5T MR magnet at
the Beth Israel Hospital, Boston, to investigate a patient with epilepsy
through correlation between EEG epileptiform abnormalities and BOLD signal
(EEG-fMRI) [1]. The initial purpose was identifying the epileptogenic focus,
defined as the brain region from which epileptic activity starts, overcoming
the low spatial resolution and incomplete spatial sampling of surface EEG [2]. Thereafter,
epilepsy was increasingly explored by the EEG-fMRI technique. First studies had
to face technical challenges. Investigators initially employed a
‘spike-triggered’ empirical approach to couple EEG and BOLD signal, starting an
Echo-Planar Imaging (EPI) sequence after direct on-line detection of an
epileptiform abnormality on EEG. The ‘spike-triggered’ approach was necessary
to avoid the perturbation of the EEG track from the electric gradient
artefactsarising into a static magnetic field [3]. However, the constant
electro-cardio-balisto-graphic artefact originated by the electric heart
activity hampered a continuous reading of the EEG track.
The EEG-fMRI technique flourished after the
development of specific subtraction algorhythms, synchronized with the EPI
sequence, that were successfully applied to remove the gradient and
electro-cardio-balisto-graphic artefactallowing a continuous reading of the EEG
track [4].
EEG-FMRI IN FOCAL EPILEPSY
After the initial experiences, focal epilepsy
appeared an ideal paradigm of study for EEG-fMRI. The technique appeared
especially attractive to investigate both patients with lesional and
non-lesional epilepsy with the aim of defining the epileptogenic focus to be
surgically removed. Hence, EEG-fMRI could chaperon nuclear medicine
investigations (PET, SPECT) as support to guide the surgical planning.
However, earlier results suggested the BOLD
correlate of EEG abnormalities did not constantly match the epileptogenic focus
as defined by depth stereo-EEG but also spread to distant brain regions [5-8].
It has been hypothesized that the low temporal
resolution of fMRI allows recording more the BOLD correlate of the spread
epileptic discharges than the initial epileptic activity [9,10]. Technical
advancements have then allowed the co-registration between fMRI and depth
stereo-EEG showing an increase of the BOLD signal both within the epileptogenic
focus and in remote areas, including the default mode network, which occurred
during both EEG interictal and ictal abnromalities [11,12]. The default mode
network (DMN) is a network usually activated at rest and deactivated after a
task, composed by interacting brain regions known to have activity highly
correlated with each other and distinct from other networks in the brain [13].
Many evidences converge on the detrimental
effect of interictal discharges on brain functional connectivity. It has
recently been demonstrated that the epileptiform discharges can especially
interfere with visual and attentional networks in focal epilepsy, irrespective
from the location of the epileptogenic focus [14]. In benign rolandic epilepsy,
epileptiform discharges would interfere with brain networks responsible for
language, behaviour, and cognition [15]. Such interferences with physiological
brain networks might underpin the negative effect of epileptic activity on
cognitive functioning.
EEG-FMRI IN GENERALIZED EPILEPSY
The identification of brain networks in focal epilepsy
prompted to investigate the generalized epilepsies. In generalized epilepsy, it
has long postulated a central role for the thalamus, which would be primarily
activated (‘centro-encephalic’ or ‘cortico-reticular’ theories) or secondarily
involved after trigger from a cortical focus (‘cortical focus’ theory) [16].
Each
generalized epilepsy exhibits relatively homogeneous characteristics and are
therefore particularly attractive to group studies.
Early
studies explored generalized spike-and-waves (GSW) discharges, irrespective
from the specific syndrome, and demonstrated a constant BOLD signal increase in
the thalamus as well as variable BOLD modifications in distant cortical regions
[17-20].
Most
deactivations involved bilaterally the mesial frontal, insula, cingulate and
parietal cortex, regions constituting the DMN. Therefore, GSW would perturb the
normal resting state of the brain [21,22].
Such
interference with the DMN has been specifically observed in childhood absence
epilepsy (CAE) and in eyelid myoclonia with absences and has been hypothesized
to underpin the altered state of consciousness in absence seizures [23-25].
Subsequent
studies in patients with GSW have observed thalamic activation preceding DMN
deactivation. On the contrary, other studies in CAE have demonstrated an
initial cortical activation (frontal or parietal) [26-28]. Szaflarski et al.
have observed early thalamic activation in drug-responsive CAE, and early
cortical activation in drug-resistant CAE [29].
Different
approaches have been subsequently developed to investigate the BOLD signal
before GSW onset. In fact, the electric onset of epileptiform abnormalities
expresses a neuronal hypersincronization that can only be measured by direct
cell recording, while epileptiform discharges on surface EEG occur later.
Following this study paradigm, DMN activation has been observed to precede GSW
onset in absence seizures [30].
EEG-fMRI
has also been applied to investigate photosensitivity in Juvenile Myoclonic
Epilepsy highlighting a BOLD signal increase in putamen before the onset of the
photoparoxysmal response, followed by thalamus activation and lately by
widespread cortical, putamen and caudate deactivation [31].
CONCLUSION
The
EEG-fMRI technique has undergone impressive technical improvements in recent
years. Several studies have demonstrated the involvement of complex neuronal
networks both in focal and generalized epilepsy. However, the relationship
between EEG and BOLD signal has not been completely elucidated. Further studies
exploring larger series, using ictal EEG abnormalities or studying the
correlation between EEG and the BOLD signal at 7T ultra-high field could
provide further advancements in non-invasively identifying the epileptic focus
and in understanding the pathophysiological substrates of generalized
epilepsies.
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- Xiao F, An D, Lei D, Li L, Chen S, et al. (2016)
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- Liu Y, Yang T, Liao W, et al. (2008) EEG-fMRI study of
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