Altered spontaneous neuronal activity of the default-mode network in mesial temporal lobe epilepsy

Abstract

Increasing evidence from behavioral and neuroimaging studies suggests that mesial temporal lobe epilepsy (mTLE) is possibly associated with the default-mode brain function. However, the alteration of coherent neural activities in such a default-mode network (DMN) in mTLE has yet to be investigated. The present study analyzed the resting-state functional MRI data from two groups of mTLE patients with left and right hippocampal sclerosis using independent component analysis. In comparison with healthy controls, decreased functional connectivity in the dorsal mesial prefrontal cortex, mesial temporal lobe and inferior temporal cortex was observed in these two patient groups. Moreover, the right but not left mTLE patients showed bilaterally decreased functional connectivity in the mesial temporal lobe and increased functional connectivity in the posterior cingulate cortex. The decreased functional connectivity of the mesial temporal lobe was related to the epilepsy duration, suggesting that the posterior cingulate cortex may play a compensatory role for the altered DMN in the right mTLE. These findings indicate that the DMN is widely affected even if a single network node is impaired. An extensive regional overlap between the DMN and the previously described epileptic network suggests that the widespread functional impairments in mTLE may attribute to an aberrant DMN. The distinct patterns of the DMN between the left and right mTLE support a view that there are different pathological mechanisms underlying these two types of epilepsies.

Introduction

Recent neuroimaging studies have documented that the default-mode network (DMN) is a specialized anatomical brain system, primarily consisting of posterior cingulate cortex (PCC)/precuneus, ventral anterior cingulate cortex (vACC)/mesial prefrontal cortex (MPFC), angular gyrus (AG), inferior temporal cortex (ITC) and mesial temporal lobes (mTL). The DMN is engaged in the maintenance of the baseline brain activities related to cognitions of self-awareness, episodic memory and interactive modulation between the internal mind activities and external tasks (Buckner et al., 2008, Fox et al., 2005, Raichle et al., 2001). Moreover, altered default-mode function has been reported to be associated with cognitive impairments in various brain abnormalities, such as in Alzheimer's disease (Greicius et al., 2004), schizophrenia (Garrity et al., 2007), attention deficit/hyperactivity disorder (Tian et al., 2006), as well as epilepsy (Archer et al., 2003, Gotman et al., 2005, Laufs et al., 2007).

Mesial temporal lobe epilepsy (mTLE) is the most common type of human epilepsy. Hippocampal sclerosis (HS) was found in a large number of mTLE patients and is speculated to be the cause of epilepsy and to be responsible for the cognitive impairment of memory in mTLE. This pathological feature makes it a unique disease model to observe the DMN alteration with regard to a focal nodal lesion in the network. MTLE often presents a few of abnormal psychological and psychiatric symptoms associated with the functionalities of the DMN (Buckner et al., 2008), such as absence of self-awareness, emotional and psychic experiences (Wieser, 2004), as well as social cognitive impairments (Jokeit and Ebner, 1999). Accordingly, the widespread cortical and subcortical abnormalities in the mTLE revealed by neuroimaging studies suggest that mTLE can be viewed as a network disease (Blumenfeld et al., 2004, Spencer, 2002). Concerning the associations of the involved behaviors between the mTLE and DMN, as well as the structural overlaps between the epileptic network and the DMN, it is thus reasonable to speculate a potential role of the DMN in the development of the clinical manifestations of mTLE.

A recent functional MRI (fMRI) study has revealed that the interictal discharges (IEDs)-related deactivation in the default-mode regions is more frequently observed as compared with that in extra-temporal lobe epilepsy (Laufs et al., 2007). It is interpreted that the IEDs, simply like a goal-directed tasks, can suspend the normal default-mode brain function, which might be a pathophysiological mechanism underlying impaired consciousness in patients with mTLE (Kobayashi et al., 2006b, Salek-Haddadi et al., 2006) and generalized epilepsy (Archer et al., 2003, Gotman et al., 2005). However, no such deactivation was found by another fMRI study of mTLE (Kobayashi et al., 2006a). The IEDs-related default-mode region deactivation reflects the instantaneous effect of the epileptic activity on the DMN. However, little is known about alteration of the DMN in mTLE from the aspect of coherent low-frequency BOLD fluctuation. The coherent fluctuation resulted from the spontaneous neuronal activity in the patients is assumed to reflect the altered intrinsic property of the DMN (Buckner et al., 2008, Greicius et al., 2004).

In the present study, we employed independent component analysis (ICA), one of the most commonly used methods in functional connectivity studies, to extract the DMN with regard to the functional connectivity of coherent spontaneous neuronal activities (Greicius et al., 2004, Greicius et al., 2007, Jafri et al., 2008) from the resting-state fMRI data of mTLE patients. Our experiments were designed to investigate: (i) the spatial pattern of altered DMN in mTLE with focal lesion of hippocampal sclerosis; (ii) the relationship between the altered DMN and the reported epileptic network involved in mTLE (Spencer, 2002); and (iii) differently altered patterns of the DMN in various lateralizing of mTLE, in light of the view that patients with the differently sided mTLE may have different underlying pathological and etiological substrates (Alessio et al., 2006, Janszky et al., 2003a, Janszky et al., 2003b, Van Paesschen et al., 1997).