Association between seizure freedom and default mode network reorganization in patients with unilateral temporal lobe epilepsy.

RATIONALE: The spontaneous synchronized activity and intrinsic organization of the Default Mode Network (DMN) has been found to be altered because of epileptic activity of temporal lobe origin. Thus, the aim of the present study was to compare DMN's topological properties in patients with seizure-free (SF) and not seizure-free (NSF) temporal lobe epilepsy (TLE). METHODS: Functional connectivity within the DMN was determined from an 8-minute resting state functional magnetic resonance imaging (fMRI) in 27 patients with TLE (12 SF, 15 NSF) and 15 healthy controls (HC). The DMN regions of interest were extracted according to the automated anatomical labeling (AAL) atlas. Network properties were assessed using standard graph-theoretical measures. RESULTS: Analyses revealed, irrespectively of focus lateralization, borderline significance for longer paths (p = 0.049) and in trend reduced local efficiency within the DMN of SF when compared with that of NSF (p = 0.075). The SF and NSF patients did not differ in global network topology from HC (p > 0.05). At the nodal network level, the degree of central hubs was significantly reduced in SF when compared with that in NSF (0.002 ≤ p ≤ 0.080) and HC (0.001 ≤ p ≤ 0.066) while simultaneously, right anterior superior temporal gyrus revealed significantly higher degree in SF than in NSF (p = 0.005) and HC (p = 0.016). CONCLUSION: Seizure freedom seems to be associated with hub redistributions that may underlie longer paths and (in trend) reduced local efficiency of the network. An associated slower system response might reduce the probability of a rapid spread of epileptic discharges over the whole network and may help to prevent hypersynchronous neuronal activity in brain networks that may result in epileptic seizures.

Cognitive and behavioral comorbidities in Rolandic epilepsy and their relation with default mode network's functional connectivity and organization.

OBJECTIVE: Rolandic epilepsy (RE) is characterized by typical interictal-electroencephalogram (EEG) patterns mainly localized in centrotemporal and parietooccipital areas. An aberrant intrinsic organization of the default mode network (DMN) due to repeated disturbances from spike-generating areas may be able to account for specific cognitive deficits and behavioral problems in RE. The aim of the present study was to investigate cognitive development (CD) and socioemotional development (SED) in patients with RE during active disease in relation to DMN connectivity and network topology. METHODS: In 10 children with RE and active EEG, CD was assessed using the Wechsler Intelligence Scale for Children-IV (WISC-IV); SED was assessed using the Fünf-Faktoren-Fragebogen für Kinder (FFFK), a Big-Five inventory for the assessment of personality traits in children. Functional connectivity (FC) in the DMN was determined from a 15-minute resting state functional magnetic resonance imaging (fMRI), and network properties were calculated using standard graph-theoretical measures. RESULTS: More severe deficits of verbal abilities tended to be associated with an earlier age at epilepsy onset, but were not directly related to the number of seizures and disease duration. Nonetheless, at the network level, disease duration was associated with alterations of the efficiency and centrality of parietal network nodes and midline structures. Particularly, centrality of the left inferior parietal lobe (IPL) was found to be linked with CD. Reduced centrality of the left IPL and alterations supporting a rather segregated processing within DMN's subsystems was associated with a more favorable CD. A more complicated SED was associated with high seizure frequency and long disease duration, and revealed links with a less favorable CD. SIGNIFICANCE: An impaired CD and - because of their interrelation - SED might be mediated by a common pathomechanism reflected in an aberrant organization, and thus, a potential functional deficit of the DMN. A functional segregation of (left) parietal network nodes from the DMN and a rather segregated processing mode within the DMN might have positive implications/protective value for CD in patients with RE.

Reduced glucose metabolism in neocortical network nodes remote from hypothalamic hamartomas reflects cognitive impairment.

The clinical appearance of patients with hypothalamic hamartomas is very heterogeneous, and interindividual variability of intellectual abilities is not completely understood. We retrospectively investigated cerebral dysfunction as indicated by reduced regional glucose metabolism in 29 patients (age range 7-49 years) with epilepsy due to hypothalamic hamartomas. Brain metabolism assessed by [18 F]FDG-PET was compared between patients with and without cognitive impairment controlled for unevenly distributed hamartoma lateralization seen on magnetic resonance imaging (MRI). Due to the broad age range, the variable "age" was included in the imaging analyses as a covariate. Additional voxel-wise analysis with hamartoma volume, disease duration, seizure severity, seizure frequency, and antiepileptic drug (AED) load as well as dosage and gender as further covariates was accomplished. Furthermore, global visual ratings on laterality of hypometabolism patterns were assessed according to clinical standards and related to hamartoma lateralization on MRI as well as lateralization of electroencephalography (EEG) abnormalities. Cognitively impaired patients showed significantly reduced glucose metabolism in bilateral frontal as well as right parietal and posterior midline cortices (p < 0.005), irrespective of hamartoma lateralization seen on MRI. Additional voxel-wise analysis with the above-mentioned further covariates revealed comparable results. FDG uptake values within the main right frontal cluster obtained from group comparison were not associated with hamartoma volume, disease duration, or AED load. Irrespective of cognitive functioning, lateralization of reduced FDG uptake in global visual ratings was associated with lateralization of hypothalamic hamartomas seen on MRI (p < 0.01), but not with EEG abnormalities. We found regions of reduced glucose metabolism in cognitively impaired patients remote from the hypothalamic hamartomas in frontal and parietal regions, which have been identified as important network nodes in the human brain and are linked to higher cognitive functions.

Flashbulb memories: Is the amygdala central? An investigation of patients with amygdalar damage.

Flashbulb memories (FM) are a subgroup of autobiographical memories referring to the circumstances in which a person first heard of a surprising, emotionally arousing event. Patients with temporal lobe epilepsy (TLE) have been reported to be impaired in FM recall. As emotional arousal is central to FM, various authors have suggested a crucial role of the amygdala. However, to date, no studies have directly addressed this hypothesis. In this study, 33 TLE patients and 20 healthy controls (HC) were tested on an FM task twice with a minimum interval of two months. FM recall quality was measured as consistency of the answers. Patients were grouped according to the presence as well as the lateralisation of amygdalar damage, using information of brain imaging and intracranial electroencephalography-recordings. Analyses revealed that, relative to HC, patients with amygdalar damage had significantly diminished FM recall quality, whereas patients with intact amygdalae did not. Particularly patients with amygdalar damage in the non-language-dominant hemisphere performed significantly worse than HC. Findings suggest a negative influence of amygdalar damage, possibly especially in the non-dominant hemisphere, on FM retrieval quality. Given the shocking character of events evoking FM, a rapid emotion detection system involving the right (i.e. non-dominant) amygdala could be influential to FM formation. Thus, the present findings support previous, not yet examined, hypotheses concerning a crucial role of the amygdala in FM.

Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesial temporal lobe epilepsy and unilateral hippocampal sclerosis.

Several studies have demonstrated the positive effect of resective epilepsy surgery in drug-resistant temporal lobe epilepsy (TLE). However, it is still a matter of debate whether selective amygdalohippocampectomy (SAH) or standard temporal lobectomy (STL) are the most effective approaches concerning seizure outcome, quality of life and memory. In each of the two centers participating in this study either SAH or STL was the neurosurgical standard procedure irrespective of contextual aspects. Thus, with this postoperative assessment of resected patients we sought to avoid any selection bias that usually impaired comparative trials of both surgical approaches. We finally identified and studied 95 adult patients who had undergone either SAH (n=46) or STL (n=49) between 1999 and 2009 and fulfilled the inclusion criteria, namely drug-resistant unilateral mesial TLE with hippocampal sclerosis without any further structural lesions. We assessed the postoperative seizure outcome according to the ILAE criteria and postoperative quality of life by means of standardized questionnaires. Finally, we compared postoperative neuropsychological performance in 60 completely seizure-free patients (n=27 after SAH, n=33 after STL) prior to, one year after surgery and at a long-term follow-up with a mean of seven years. 78.2% of SAH and 85.7% of STL were seizure-free at the last observation. Quality of life had improved in 95.6% of the SAH patients and 89.8% of the STL patients. These differences were not statistically significant. Left-sided TLE patients had a significantly worse verbal memory outcome irrespective of the surgical method. However, SAH patients had a significantly better outcome concerning visual encoding, verbal and visual short-term memory and visual working memory. In this study, seizure outcome and quality of life did not differ depending on the surgical approach. However, a more selective resection led to better neuropsychological performances.