Andréa Alessio

Asymmetrical hippocampal connectivity in mesial temporal lobe epilepsy: evidence from resting state fMRI

BackgroundMesial temporal lobe epilepsy (MTLE), the most common type of focal epilepsy in adults, is often caused by hippocampal sclerosis (HS). Patients with HS usually present memory dysfunction, which is material-specific according to the hemisphere involved and has been correlated to the degree of HS as measured by postoperative histopathology as well as by the degree of hippocampal atrophy on magnetic resonance imaging (MRI). Verbal memory is mostly affected by left-sided HS, whereas visuo-spatial memory is more affected by right HS. Some of these impairments may be related to abnormalities of the network in which individual hippocampus takes part. Functional connectivity can play an important role to understand how the hippocampi interact with other brain areas. It can be estimated via functional Magnetic Resonance Imaging (fMRI) resting state experiments by evaluating patterns of functional networks. In this study, we investigated the functional connectivity patterns of 9 control subjects, 9 patients with right MTLE and 9 patients with left MTLE.ResultsWe detected differences in functional connectivity within and between hippocampi in patients with unilateral MTLE associated with ipsilateral HS by resting state fMRI. Functional connectivity resulted to be more impaired ipsilateral to the seizure focus in both patient groups when compared to control subjects. This effect was even more pronounced for the left MTLE group.ConclusionsThe findings presented here suggest that left HS causes more reduction of functional connectivity than right HS in subjects with left hemisphere dominance for language.

Differences in memory performance and other clinical characteristics in patients with mesial temporal lobe epilepsy with and without hippocampal atrophy

Mesial temporal lobe epilepsy (MTLE) is usually accompanied by memory deficits due to damage to the hippocampal system. In most studies, however, the influence of hippocampal atrophy (HA) is confounded with other variables, such as: type of initial precipitating injury and pathological substrate, effect of lesion (HA) lateralization, history of febrile seizures, status epilepticus, age of seizure onset, duration of epilepsy, seizure frequency, and antiepileptic drugs (AEDs). To investigate the relationship between memory deficits and these variables, we studied 20 patients with MTLE and signs of HA on MRI and 15 MTLE patients with normal high-resolution MRI. The findings indicated that (1) HA, earlier onset of seizures, longer duration of epilepsy, higher seizure frequency, and AEDs (polytherapy) are associated with memory deficits; and (2) there is a close relationship between deficits of verbal memory and left HA, but not between visual memory and right HA.

Memory and language impairments and their relationships to hippocampal and perirhinal cortex damage in patients with medial temporal lobe epilepsy

Chronic medial temporal lobe epilepsy (MTLE) is associated with memory loss due to damage in the hippocampal system. To investigate the relationship between volume of medial temporal lobe structures and performance on neuropsychological tests, we studied 39 consecutive patients with MTLE and unilateral hippocampal atrophy (HA) determined by volumetric magnetic resonance imaging (MRI). Structures of interest comprised hippocampus, amygdala, and entorhinal, perirhinal, parahippocampal, and temporopolar cortices. The findings indicated that (1) performance was significantly worse in the group with left HA as compared with the group with right HA on general memory, verbal memory, delayed recall, and verbal fluency tests and the Boston Naming Test (BNT), and (2) the volume of the left hippocampus and also the degree of asymmetry of perirhinal cortex volume were significant and independent predictors of performance on general memory, verbal memory, and verbal fluency tests and the BNT in patients with MTLE.

Extrahippocampal gray matter atrophy and memory impairment in patients with medial temporal lobe epilepsy

Memory impairment observed in patients with medial temporal lobe epilepsy (MTLE) is classically attributed to hippocampal atrophy. The contribution of extrahippocampal structures in shaping memory impairment in patients with MTLE is not yet completely understood, even though atrophy in MTLE extends beyond the hippocampus. We aimed to evaluate the neuropsychological profile of patients with MTLE focusing on memory, and to investigate whether gray matter concentration (GMC) distribution within and outside the medial portion of the temporal lobes would be associated with their neuropsychological performance. We performed a voxel based morphometry study of 36 consecutive patients with MTLE and unilateral hippocampal atrophy. We observed a significant simple regression between general and verbal memory performance based on Wechsler Memory Scale—Revised and the GMC of medial temporal and extratemporal structures in patients with left MTLE. We also performed a “regions of interest analysis” of the medial temporal lobe, and we observed that the GMC of the hippocampus, entorhinal, and perirhinal cortices were consistently associated with general and verbal memory performance in patients with MTLE. We also observed that the GMC of the cingulate and orbito‐frontal cortex are independently associated with verbal and general memory performances. Our results suggest that general and verbal memory impairments in patients with left MTLE are associated with atrophy of the hippocampus, the entorhinal, and the perirhinal cortex. We also suggest that atrophy and dysfunction of limbic and frontal structures such as the cingulate and the orbito‐frontal cortex contribute to memory impairment in MTLE. Hum Brain Mapp 2007.

Brain plasticity for verbal and visual memories in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: an fMRI study.

We aimed to identify the brain areas involved in verbal and visual memory processing in normal controls and patients with unilateral mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS) by means of functional magnetic resonance imaging (fMRI). The sample comprised nine normal controls, eight patients with right MTLE, and nine patients with left MTLE. All subjects underwent fMRI with verbal and visual memory paradigms, consisting of encoding and immediate recall of 17 abstract words and 17 abstract drawings. A complex network including parietal, temporal, and frontal cortices seems to be involved in verbal memory encoding and retrieval in normal controls. Although similar areas of activation were identified in both patient groups, the extension of such activations was larger in the left‐HS group. Patients with left HS also tended to exhibit more bilateral or right lateralized encoding related activations. This finding suggests a functional reorganization of verbal memory processing areas in these patients due to the failure of left MTL system. As regards visual memory encoding and retrieval, our findings support the hypothesis of a more diffuse and bilateral representation of this cognitive function in the brain. Compared to normal controls, encoding in the left‐HS group recruited more widespread cortical areas, which were even more widespread in the right‐HS group probably to compensate for their right mesial temporal dysfunction. In contrast, the right‐HS group exhibited fewer activated areas during immediate recall than the other two groups, probably related to their greater difficulty in dealing with visual memory content. Hum Brain Mapp, 2013.

Evidence of memory impairment in asymptomatic individuals with hippocampal atrophy

Our objective was to investigate if MRI-determined hippocampal atrophy (HA) is associated with memory deficits independent of seizure frequency. We studied three groups of individuals: (1) 10 asymptomatic first-degree relatives of patients with familial mesial temporal lobe epilepsy (FMTLE), all of them with HA; (2) 14 patients with benign FMTLE, 9 with HA, and 5 with normal hippocampal volumes; and (3) 16 patients with refractory FMTLE, all but one with HA. HA was associated with lower scores on general memory (P=0.015), verbal memory (P=0.020), and delayed recall (P=0.028), even in those with no or few seizures in life. General linear model analyses showed that the interaction between seizure outcome and HA was associated with worse verbal memory (P=0.029), visual memory (P=0.022), and delayed recall (P=0.039) as compared with each of these factors independently. Our findings suggest that seizures and HA are independently associated with memory impairment.

Long-term postoperative atrophy of contralateral hippocampus and cognitive function in unilateral refractory MTLE with unilateral hippocampal sclerosis

OBJECTIVE This study aimed to evaluate long-term atrophy in contralateral hippocampal volume after surgery for unilateral MTLE, as well as the cognitive outcome for patients submitted to either selective transsylvian amygdalohippocampectomy (SelAH) or anterior temporal lobe resection (ATL). METHODS We performed a longitudinal study of 47 patients with MRI signs of unilateral hippocampal sclerosis (23 patients with right-sided hippocampal sclerosis) who underwent surgical treatment for MTLE. They underwent preoperative/postoperative high-resolution MRI as well as neuropsychological assessment for memory and estimated IQ. To investigate possible changes in the contralateral hippocampus of patients, we included 28 controls who underwent two MRIs at long-term intervals. RESULTS The volumetry using preoperative MRI showed significant hippocampal atrophy ipsilateral to the side of surgery when compared with controls (p<0.0001) but no differences in contralateral hippocampal volumes. The mean postoperative follow-up was 8.7 years (± 2.5 SD; median=8.0). Our patients were classified as Engel I (80%), Engel II (18.2%), and Engel III (1.8%). We observed a small but significant reduction in the contralateral hippocampus of patients but no volume changes in controls. Most of the patients presented small declines in both estimated IQ and memory, which were more pronounced in patients with left TLE and in those with persistent seizures. Different surgical approaches did not impose differences in seizure control or in cognitive outcome. CONCLUSIONS We observed small declines in cognitive scores with most of these patients, which were worse in patients with left-sided resection and in those who continued to suffer from postoperative seizures. We also demonstrated that manual volumetry can reveal a reduction in volume in the contralateral hippocampus, although this change was mild and could not be detected by visual analysis. These new findings suggest that dynamic processes continue to act after the removal of the hippocampus, and further studies with larger groups may help in understanding the underlying mechanisms.

EEG spike source localization before and after surgery for temporal lobe epilepsy: a BOLD EEG-fMRI and independent component analysis study

Simultaneous measurements of EEG-functional magnetic resonance imaging (fMRI) combine the high temporal resolution of EEG with the distinctive spatial resolution of fMRI. The purpose of this EEG-fMRI study was to search for hemodynamic responses (blood oxygen level-dependent--BOLD responses) associated with interictal activity in a case of right mesial temporal lobe epilepsy before and after a successful selective amygdalohippocampectomy. Therefore, the study found the epileptogenic source by this noninvasive imaging technique and compared the results after removing the atrophied hippocampus. Additionally, the present study investigated the effectiveness of two different ways of localizing epileptiform spike sources, i.e., BOLD contrast and independent component analysis dipole model, by comparing their respective outcomes to the resected epileptogenic region. Our findings suggested a right hippocampus induction of the large interictal activity in the left hemisphere. Although almost a quarter of the dipoles were found near the right hippocampus region, dipole modeling resulted in a widespread distribution, making EEG analysis too weak to precisely determine by itself the source localization even by a sophisticated method of analysis such as independent component analysis. On the other hand, the combined EEG-fMRI technique made it possible to highlight the epileptogenic foci quite efficiently.

Characterization of the NIRS Hemodynamic Response Function with Independent Component Analysis

We propose an algorithm with objective criteria to identify the hemodynamic response function by using independent component analysis during cerebral activation with NIRS. The algorithm was successfully validated in both real data and simulations.