Qifu Li

Altered functional connectivity in default mode network in absence epilepsy: A resting‐state fMRI study

Dysfunctional default mode network (DMN) has been observed in various mental disorders, including epilepsy (see review Broyd et al. [ 2009 ]: Neurosci Biobehav Rev 33:279–296). Because interictal epileptic discharges may affect DMN, resting‐state fMRI was used in this study to determine DMN functional connectivity in 14 healthy controls and 12 absence epilepsy patients. To avoid interictal epileptic discharge effects, testing was performed within interictal durations when there were no interictal epileptic discharges. Cross‐correlation functional connectivity analysis with seed at posterior cingulate cortex, as well as region‐wise calculation in DMN, revealed decreased integration within DMN in the absence epilepsy patients. Region‐wise functional connectivity among the frontal, parietal, and temporal lobe was significantly decreased in the patient group. Moreover, functional connectivity between the frontal and parietal lobe revealed a significant negative correlation with epilepsy duration. These findings indicated DMN abnormalities in patients with absence epilepsy, even during resting interictal durations without interictal epileptic discharges. Abnormal functional connectivity in absence epilepsy may reflect abnormal anatomo‐functional architectural integration in DMN, as a result of cognitive mental impairment and unconsciousness during absence seizure. Hum Brain Mapp, 2011.

Resting State Basal Ganglia Network in Idiopathic Generalized Epilepsy

The basal ganglia, a brain structure related to motor control, is implicated in the modulation of epileptic discharges generalization in patients with idiopathic generalized epilepsy (IGE). Using group independent component analysis (ICA) on resting‐state fMRI data, this study identified a resting state functional network that predominantly consisted of the basal ganglia in both healthy controls and patients with IGE. In order to gain a better understanding of the basal ganglia network(BGN) in IGE patients, we compared the BGN functional connectivity of controls with that of epilepsy patients, either with interictal epileptic discharges (with‐discharge period, WDP) or without epileptic discharge (nondischarge period, NDP) while scanning. Compared with controls, functional connectivity of BGN in IGE patients demonstrated significantly more integration within BGN except cerebellum and supplementary motor area (SMA) during both periods. Compared with the NDP group, the increased functional connectivity was found in bilateral caudate nucleus and the putamen, and decreases were observed in the bilateral cerebellum and SMA in WDP group. In accord with the proposal that the basal ganglia modulates epileptic discharge activity, the results showed that the modulation enhanced the integration in BGN of patients, and modulation during WDP was stronger than that during NDP. Furthermore, reduction of functional connectivity in cerebellum and SMA, the abnormality might be further aggravated during WDP, was consistent with the behavioral manifestations with disturbed motor function in IGE. These resting‐state fMRI findings in the current study provided evidence confirming the role of the BGN as an important modulator in IGE. Hum Brain Mapp, 2011.

EEG—fMRI study on the interictal and ictal generalized spike-wave discharges in patients with childhood absence epilepsy

BACKGROUND Absence epilepsy is characterized clinically by the impairment of consciousness and 3 Hz generalized spike-wave discharges (GSWDs) on EEG. Clinical absence can be observed with ictal GSWDs, but interictal GSWD bursts are usually clinically silent. Simultaneous EEG and blood-oxygen-level-dependent (BOLD) functional MRI (EEG-fMRI) has been successfully used to link the changes in regional neuronal activity to the occurrence of GSWDs. METHODS We used EEG-fMRI to investigate and compare the BOLD signal changes during interictal and ictal GSWDs in patients with childhood absence epilepsy (CAE). RESULTS Fifteen drug-naïve children with newly diagnosed CAE were studied using continuous EEG-fMRI. BOLD signal changes associated with interictal (nine sessions with six patients) and ictal (eight sessions with six patients) GSWDs were analyzed at the individual and group levels. GSWDs were associated with widespread and symmetrical deactivation in the cortex and caudate nucleus with a frontal maximum, and predominant activation in the thalamus bilaterally during ictal GSWDs and in the cortex during interictal GSWDs. The BOLD response was characterized by a higher statistical significance and a more widespread extent at the time of the ictal GSWDs as compared to the time of interictal GSWDs. CONCLUSIONS Both interictal and ictal GSWDs in patients with CAE are associated with BOLD signal changes in the basal ganglia-thalamocortical loop. Ictal GSWDs showing predominant thalamic activation and widespread cortical deactivation might cause a complete suspension of the normal brains default state and manifest clinically as abrupt loss of consciousness (absence seizures).

Resting-state fMRI study of treatment-naïve temporal lobe epilepsy patients with depressive symptoms.

BACKGROUND Patients with temporal lobe epilepsy are at high risk for comorbid depression, and it is hypothesized that these two diseases are share common pathogenic pathways. We aimed to characterize regional brain activation in treatment-naïve temporal lobe epilepsy patients with depressive symptoms and compare the results to epilepsy patients without depressive symptoms and to healthy controls. SUBJECTS AND METHODS We recruited 23 treatment-naïve patients (including anti-epilepsy drugs (AEDs) and antidepressants) and 17 matched healthy controls for this study. The patients were further divided into two groups: patients with depressive symptoms and patients without; the patients then used a self-rating depression scale (SDS) to assess their depression. All participants underwent resting functional magnetic resonance imaging (fMRI) scans using the Trio Tim magnetic resonance (MR) image system (3.0 T). The data were processed and analyzed using REST and SPSS11.5 software. RESULTS The patients with depressive symptoms showed significantly higher activity in the bilateral thalamus, insula and caudate and right anterior cingulate compared with the two other groups (p<0.05, corrected). Brain network connectivity analysis revealed that connectivity decreased in the prefrontal-limbic system and increased within the limbic system and angular gyrus in patients with depressive symptoms (p<0.05, corrected). CONCLUSION The epilepsy patients with depressive symptoms showed regional brain activity alterations and disruption of the mood regulation network at the onset of seizures. The present study offers further insight into the underlying neuropathophysiology of epilepsy with depressive symptoms.

White matter impairment in the basal ganglia-thalamocortical circuit of drug-naïve childhood absence epilepsy

PURPOSE It is unknown whether white matter abnormalities exist in childhood absence epilepsy (CAE), a syndrome of idiopathic epilepsy (IGE). Diffusion tensor imaging (DTI) can noninvasively quantify white matter integrity. This study used DTI to investigate abnormal changes in white matter of untreated CAE patients. METHODS Subjects included nine patients with untreated CAE and nine age-and sex-matched healthy controls. Diffusion tensor imaging parameters were voxel based and statistically compared between patients and controls. The correlations between DTI parameters in regions of interest (ROIs) and age of seizure onset or duration of epilepsy were analyzed. RESULTS Untreated CAE patients had a significantly higher fractional anisotropy (FA) value in the bilateral thalamus, anterior corpus callosum and upper brainstem, while also displaying a lower FA value in prefrontal white matter, anterior cingulate, and bilateral posterior limbs of the internal capsule compared to control subjects. An increase in mean diffusivity (MD) value was observed in parietal lobe white matter, prefrontal white matter, and posterior cerebellar hemispheres, in addition to subcortical structures including bilateral putamen and posterior limb of internal capsule. MD significant correlations between ROI diffusion parameters and the duration of the disease or the age of onset. CONCLUSIONS The results showed white matter integrity impairment in the basal ganglia-thalamocortical circuit of drug-naïve CAE patients. These abnormalities in white matter may be related to increased cortical excitability and cause cognitive, linguistic, and behavioral/emotional deficits both during and between seizures.

Diffusion and volumetry abnormalities in subcortical nuclei of patients with absence seizures

Purpose:  The thalamus and basal ganglia play an important role in the propagation and modulation of generalized spike and slow‐wave discharges (SWDs) in absence epilepsy. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique sensitive to microstructural abnormalities of cerebral tissue by quantification of diffusion parameter. The purpose of this study is to investigate the diffusion and volume changes in the basal ganglia and thalamus of patients with absence seizures.

Altered Resting-State Connectivity During Interictal Generalized Spike-Wave Discharges in Drug-Naive Childhood Absence Epilepsy

Purpose: To investigate the intrinsic brain connections at the time of interictal generalized spike‐wave discharges (GSWDs) to understand their mechanism of effect on brain function in untreated childhood absence epilepsy (CAE). Methods: The EEG‐functional MRI (fMRI) was used to measure the resting state functional connectivity during interictal GSWDs in drug‐naïve CAE, and three different brain networks—the default mode network (DMN), cognitive control network (CCN), and affective network (AN)—were investigated. Results: Cross‐correlation functional connectivity analysis with priori seed revealed decreased functional connectivity within each of these three networks in the CAE patients during interictal GSWDS. It included precuneus‐dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and inferior parietal lobule in the DMN; DLPFC‐inferior frontal junction (IFJ), and pre‐supplementary motor area (pre‐SMA) subregions connectivity disruption in CCN; ACC‐ventrolateral prefrontal cortex (VLPFC) and DMPFC in AN; There were also some regions, primarily the parahippcampus, paracentral in AN, and the left frontal mid orb in the CCN, which showed increased connectivity. Conclusions: The current findings demonstrate significant alterations of resting‐state networks in drug naïve CAE subjects during interictal GSWDs and interictal GSWDs can cause dysfunction in specific networks important for psychosocial function. Impairment of these networks may cause deficits both during and between seizures. Our study may contribute to the understanding of neuro‐pathophysiological mechanism of psychosocial function impairments in patients with CAE. Hum Brain Mapp, 2013.

Altered intrinsic functional connectivity of the salience network in childhood absence epilepsy

Intrinsic connectivity analysis provides an original way for evaluating functional impairments in epilepsy. Disturbances in the salience network (SN) have been positing an important interplay in disorders of consciousness and attention. This study aims to assess the intrinsic connectivity of the SN in childhood absence epilepsy (CAE). Resting state fMRI was performed in 21 patients with CAE and 21 healthy controls. The SN was extracted using group independent component analysis with dual-regression. Intrinsic functional integration was evaluated through voxelwise comparisons between patients and controls. Patients showed a decreased functional integration of the SN in the right anterior insula, anterior temporoparietal junction, and bilateral dorsolateral frontal cortex and increased connectivity in the anterior and middle cingulate gyrus and caudate nuclei. A leftward lateralization was observed in the anterior insula and anterior temporoparietal junction in CAE. Moreover, the lateralized index in the anterior insula was significantly correlated with the duration of epilepsy. These results support the disturbance of intrinsic activity in the SN which may be linked to the interruption of salient information processing and associated with the attentional dysfunction in CAE. Our findings demonstrate the potential value of intrinsic activity in the SN for the investigation of attention process and may help to better understand the association between intrinsic activity in the SN and consciousness.

Altered resting state functional network connectivity in children absence epilepsy

Altered functional connectivity has been associated with the influence of epileptic activity. Abnormalities in connectivity, particularly in dorsal attention (DAN), salience (SN) and default mode (DMN) networks, might contribute to the loss of consciousness during seizures and cognitive deficits in patients with children absence epilepsy (CAE). The objective of the present study was to identify whether the functional network connectivity (FNC) is changed between patients with CAE and healthy controls. Using independent component analysis, twelve resting state networks (RSNs) were identified in resting state functional magnetic resonance imaging data sets in eighteen CAE patients and twenty-one healthy controls. Analyses of the group differences in FNC strength were conducted, controlling for age and gender effects. The findings showed that some functional networks were clustered into two subgroups, correlated within subgroups and antagonized with each other. Compared with the controls, patients with CAE demonstrated abnormal FNC strength among three networks: DMN, DAN and SN. In addition, the antagonism of two subgroups was altered. These results might reflect the underlying neuronal functional impairment or altered integration among these RSNs in CAE, suggesting that the abnormal functional connectivity is likely to imply the pathological mechanism associated with the accumulative influence of epileptic activity. These findings contribute to the understanding of the behavior abnormality in CAE, such as disturbed executive and attentional functions and the loss of consciousness during absence seizures.

Imaging foci of epileptic discharges from simultaneous EEG and fMRI using the canonical HRF.

PURPOSE Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) is considered as a powerful and non-invasive method that allows definition of the irritative zone. However, the complex interictal epileptic discharge (IED) may be present in some patients, and sometimes no active foci can be localized using General Linear Model (GLM) which is a widely adopted tool in EEG-fMRI study. The purpose of this study is to develop a new scheme to improve the detectability and localize the canonical HRF localizable foci. METHOD Various IEDs are classified using a combination of an independent component analysis (ICA) and a temporal correlation analysis between the independent components and the raw EEG channel; and the classified IEDs are then separately used for foci localization. This scheme is tested by ten patients with variable IEDs, including two patients whose activity could not be identified by common method. RESULT Applying this scheme to the two patients, some foci consistent with electroclinical data were localized. When it was applied to the remaining eight patients with positive results using common method, 2-4 types of IEDs were classified, and the activity could be identified from at least one type of IED. The results were similar to that received from common method. CONCLUSION These results indicate that the proposed scheme could enhance the imaging of the localizable foci by isolating its IEDs. This scheme is potentially a useful tool for epilepsy clinic.