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Insights into the mechanisms of absence seizure generation provided by EEG with functional MRI.

Carney PW, Jackson GD - Front Neurol (2014)

Bottom Line: The main component displaying an increase in blood oxygen level dependent (BOLD) signal relative to the resting state, in group studies, is the thalamus while the most consistent cortical change is reduced BOLD signal in the DMN.This region also shows altered FC in patients with AS.Hence, it appears that engagement of this network is central to AS.

View Article: PubMed Central - PubMed

Affiliation: The Florey Institute for Neuroscience and Mental Health , Heidelberg, VIC , Australia ; The University of Melbourne , Parkville, VIC , Australia ; Austin Health , Heidelberg, VIC , Australia.

ABSTRACT
Absence seizures (AS) are brief epileptic events characterized by loss of awareness with subtle motor features. They may be very frequent, and impact on attention, learning, and memory. A number of pathophysiological models have been developed to explain the mechanism of absence seizure generation, which relies heavily on observations from animal studies. Studying the structural and functional relationships between large-scale brain networks in humans is only practical with non-invasive whole brain techniques. EEG with functional MRI (EEG-fMRI) is one such technique that provides an opportunity to explore the interactions between brain structures involved in AS generation. A number of fMRI techniques including event-related analysis, time-course analysis, and functional connectivity (FC) have identified a common network of structures involved in AS. This network comprises the thalamus, midline, and lateral parietal cortex [the default mode network (DMN)], caudate nuclei, and the reticular structures of the pons. The main component displaying an increase in blood oxygen level dependent (BOLD) signal relative to the resting state, in group studies, is the thalamus while the most consistent cortical change is reduced BOLD signal in the DMN. Time-course analysis shows that, rather than some structures being activated or inactivated during AS, there appears to be increase in activity across components of the network preceding or following the electro-clinical onset of the seizure. The earliest change in BOLD signal occurs in the DMN, prior to the onset of epileptiform events. This region also shows altered FC in patients with AS. Hence, it appears that engagement of this network is central to AS. In this review, we will explore the insights of EEG-fMRI studies into the mechanisms of AS and consider how the DMN is likely to be the major large-scale brain network central to both seizure generation and seizure manifestations.

No MeSH data available.


Related in: MedlinePlus

BOLD signal change for three subjects showing variability of cortical BOLD change (figure previously unpublished). Color maps of positive BOLD (red to white: 0 to +10) and negative BOLD (blue to green: 0 to −10) change superimposed on subjects mean EPI image are displayed in three plains (p < 0.001). A single surface rendered image is also displayed demonstrating the cortical surface involved. Subject 1: 16 years female with onset of AS at age 5 who developed refractory AS and GTCS. EEG-fMRI of 6 (14 s) bursts of interictal activity. Subject 2: 13 years male with onset of AS at age 8 who achieved seizure control on mono-therapy. EEG-fMRI of 11 AS (105 s). Subject 3: 5 years female with AS since 4 who achieved seizure control on mono-therapy. EEG-fMRI of 6 AS (83 s).
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Figure 4: BOLD signal change for three subjects showing variability of cortical BOLD change (figure previously unpublished). Color maps of positive BOLD (red to white: 0 to +10) and negative BOLD (blue to green: 0 to −10) change superimposed on subjects mean EPI image are displayed in three plains (p < 0.001). A single surface rendered image is also displayed demonstrating the cortical surface involved. Subject 1: 16 years female with onset of AS at age 5 who developed refractory AS and GTCS. EEG-fMRI of 6 (14 s) bursts of interictal activity. Subject 2: 13 years male with onset of AS at age 8 who achieved seizure control on mono-therapy. EEG-fMRI of 11 AS (105 s). Subject 3: 5 years female with AS since 4 who achieved seizure control on mono-therapy. EEG-fMRI of 6 AS (83 s).

Mentions: As discussed above, it would be expected that BOLD signal change would be seen in the frontal cortex as a consistent finding, given the observations made in animal models, as well as observations from electrophysiology. Negative BOLD change has been identified in the mesial frontal and anterior cingulate cortex in several studies (55, 56, 65, 66), which is not surprising given this region is a component of the DMN. Focal cortical BOLD change may be seen in individual cases (55, 65, 68), and it has been suggested that there may be subject specific changes in BOLD signal, which are consistent within individuals but vary from subject to subject (68). Another possibility is that frontal cortical BOLD change may reflect differences in sub-groups of patients with absence epilepsy (66). What is clear is that BOLD signal in the frontal lobe is influenced by AS (see Figure 4 for individual case results). When using a standardized event-related analysis of a group or individual, this may appear as increases, decreases, or no change. However, in group and individual analyses of BOLD time course, there are clear increases in BOLD signal in frontal cortical networks occurring prior to, co-incident with, or following the event onset. This is highlighted in our paper on sub-group differences in frontal cortical BOLD in which the division into frontal negative or frontal positive was dependent on the timing of the BOLD signal increase relative to the event onset, not whether BOLD signal increased or decreased (66). Given the wealth of clinical, electrophysiological, and functional data highlighting the importance of frontal lobe activity in seizure generation, it is important for fMRI techniques to better explore the contribution of frontal lobes to seizure generation.


Insights into the mechanisms of absence seizure generation provided by EEG with functional MRI.

Carney PW, Jackson GD - Front Neurol (2014)

BOLD signal change for three subjects showing variability of cortical BOLD change (figure previously unpublished). Color maps of positive BOLD (red to white: 0 to +10) and negative BOLD (blue to green: 0 to −10) change superimposed on subjects mean EPI image are displayed in three plains (p < 0.001). A single surface rendered image is also displayed demonstrating the cortical surface involved. Subject 1: 16 years female with onset of AS at age 5 who developed refractory AS and GTCS. EEG-fMRI of 6 (14 s) bursts of interictal activity. Subject 2: 13 years male with onset of AS at age 8 who achieved seizure control on mono-therapy. EEG-fMRI of 11 AS (105 s). Subject 3: 5 years female with AS since 4 who achieved seizure control on mono-therapy. EEG-fMRI of 6 AS (83 s).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150362&req=5

Figure 4: BOLD signal change for three subjects showing variability of cortical BOLD change (figure previously unpublished). Color maps of positive BOLD (red to white: 0 to +10) and negative BOLD (blue to green: 0 to −10) change superimposed on subjects mean EPI image are displayed in three plains (p < 0.001). A single surface rendered image is also displayed demonstrating the cortical surface involved. Subject 1: 16 years female with onset of AS at age 5 who developed refractory AS and GTCS. EEG-fMRI of 6 (14 s) bursts of interictal activity. Subject 2: 13 years male with onset of AS at age 8 who achieved seizure control on mono-therapy. EEG-fMRI of 11 AS (105 s). Subject 3: 5 years female with AS since 4 who achieved seizure control on mono-therapy. EEG-fMRI of 6 AS (83 s).
Mentions: As discussed above, it would be expected that BOLD signal change would be seen in the frontal cortex as a consistent finding, given the observations made in animal models, as well as observations from electrophysiology. Negative BOLD change has been identified in the mesial frontal and anterior cingulate cortex in several studies (55, 56, 65, 66), which is not surprising given this region is a component of the DMN. Focal cortical BOLD change may be seen in individual cases (55, 65, 68), and it has been suggested that there may be subject specific changes in BOLD signal, which are consistent within individuals but vary from subject to subject (68). Another possibility is that frontal cortical BOLD change may reflect differences in sub-groups of patients with absence epilepsy (66). What is clear is that BOLD signal in the frontal lobe is influenced by AS (see Figure 4 for individual case results). When using a standardized event-related analysis of a group or individual, this may appear as increases, decreases, or no change. However, in group and individual analyses of BOLD time course, there are clear increases in BOLD signal in frontal cortical networks occurring prior to, co-incident with, or following the event onset. This is highlighted in our paper on sub-group differences in frontal cortical BOLD in which the division into frontal negative or frontal positive was dependent on the timing of the BOLD signal increase relative to the event onset, not whether BOLD signal increased or decreased (66). Given the wealth of clinical, electrophysiological, and functional data highlighting the importance of frontal lobe activity in seizure generation, it is important for fMRI techniques to better explore the contribution of frontal lobes to seizure generation.

Bottom Line: The main component displaying an increase in blood oxygen level dependent (BOLD) signal relative to the resting state, in group studies, is the thalamus while the most consistent cortical change is reduced BOLD signal in the DMN.This region also shows altered FC in patients with AS.Hence, it appears that engagement of this network is central to AS.

View Article: PubMed Central - PubMed

Affiliation: The Florey Institute for Neuroscience and Mental Health , Heidelberg, VIC , Australia ; The University of Melbourne , Parkville, VIC , Australia ; Austin Health , Heidelberg, VIC , Australia.

ABSTRACT
Absence seizures (AS) are brief epileptic events characterized by loss of awareness with subtle motor features. They may be very frequent, and impact on attention, learning, and memory. A number of pathophysiological models have been developed to explain the mechanism of absence seizure generation, which relies heavily on observations from animal studies. Studying the structural and functional relationships between large-scale brain networks in humans is only practical with non-invasive whole brain techniques. EEG with functional MRI (EEG-fMRI) is one such technique that provides an opportunity to explore the interactions between brain structures involved in AS generation. A number of fMRI techniques including event-related analysis, time-course analysis, and functional connectivity (FC) have identified a common network of structures involved in AS. This network comprises the thalamus, midline, and lateral parietal cortex [the default mode network (DMN)], caudate nuclei, and the reticular structures of the pons. The main component displaying an increase in blood oxygen level dependent (BOLD) signal relative to the resting state, in group studies, is the thalamus while the most consistent cortical change is reduced BOLD signal in the DMN. Time-course analysis shows that, rather than some structures being activated or inactivated during AS, there appears to be increase in activity across components of the network preceding or following the electro-clinical onset of the seizure. The earliest change in BOLD signal occurs in the DMN, prior to the onset of epileptiform events. This region also shows altered FC in patients with AS. Hence, it appears that engagement of this network is central to AS. In this review, we will explore the insights of EEG-fMRI studies into the mechanisms of AS and consider how the DMN is likely to be the major large-scale brain network central to both seizure generation and seizure manifestations.

No MeSH data available.


Related in: MedlinePlus