EEG-fMRI in the presurgical evaluation of temporal lobe epilepsy.

OBJECTIVE: Drug-resistant temporal lobe epilepsy (TLE) often requires thorough investigation to define the epileptogenic zone for surgical treatment. We used simultaneous interictal scalp EEG-fMRI to evaluate its value for predicting long-term postsurgical outcome. METHODS: 30 patients undergoing presurgical evaluation and proceeding to temporal lobe (TL) resection were studied. Interictal epileptiform discharges (IEDs) were identified on intra-MRI EEG and used to build a model of haemodynamic changes. In addition, topographic electroencephalographic correlation maps were calculated between the average IED during video-EEG and intra-MRI EEG, and used as a condition. This allowed the analysis of all data irrespective of the presence of IED on intra-MRI EEG. Mean follow-up after surgery was 46 months. International League Against Epilepsy (ILAE) outcomes 1 and 2 were considered good, and 3-6 poor, surgical outcome. Haemodynamic maps were classified according to the presence (Concordant) or absence (Discordant) of Blood Oxygen Level-Dependent (BOLD) change in the TL overlapping with the surgical resection. RESULTS: The proportion of patients with good surgical outcome was significantly higher (13/16; 81%) in the Concordant than in the Discordant group (3/14; 21%) (χ(2) test, Yates correction, p=0.003) and multivariate analysis showed that Concordant BOLD maps were independently related to good surgical outcome (p=0.007). Sensitivity and specificity of EEG-fMRI results to identify patients with good surgical outcome were 81% and 79%, respectively, and positive and negative predictive values were 81% and 79%, respectively. INTERPRETATION: The presence of significant BOLD changes in the area of resection on interictal EEG-fMRI in patients with TLE retrospectively confirmed the epileptogenic zone. Surgical resection including regions of haemodynamic changes in the TL may lead to better postoperative outcome.

Pattern changes of EEG oscillations and BOLD signals associated with temporal lobe epilepsy as revealed by a working memory task.

BACKGROUND: It is known that the abnormal neural activity in epilepsy may be associated to the reorganization of neural circuits and brain plasticity in various ways. On that basis, we hypothesized that changes in neuronal circuitry due to epilepsy could lead to measurable variations in patterns of both EEG and BOLD signals in patients performing some cognitive task as compared to what would be obtained in normal condition. Thus, the aim of this study was to compare the cerebral areas involved in EEG oscillations versus fMRI signal patterns during a working memory (WM) task in normal controls and patients with refractory mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS). The study included six patients with left MTLE-HS (left-HS group) and seven normal controls (control group) matched to the patients by age and educational level, both groups undergoing a blocked design paradigm based on Sternberg test during separated EEG and fMRI sessions. This test consisted of encoding and maintenance of a variable number of consonant letters on WM. RESULTS: EEG analysis for the encoding period revealed the presence of theta and alpha oscillations in the frontal and parietal areas, respectively. Likewise, fMRI showed the co-occurrence of positive and negative BOLD signals in both brain regions. As for the maintenance period, whereas EEG analysis revealed disappearance of theta oscillation, fMRI showed decrease of positive BOLD in frontal area and increase of negative BOLD in the posterior part of the brain. CONCLUSIONS: Generally speaking, these patterns of electrophysiological and hemodynamic signals were observed for both control and left-HS groups. However, the data also revealed remarkable differences between these groups that are consistent with the hypothesis of reorganization of brain circuitry associated with epilepsy.

Distinct functional and structural MRI abnormalities in mesial temporal lobe epilepsy with and without hippocampal sclerosis.

OBJECTIVE: We aimed to investigate patterns of electroencephalography-correlated functional MRI (EEG-fMRI) and subtle structural abnormalities in patients with mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (MTLE-HS) or normal MRI (MTLE-NL). METHODS: We evaluated EEG-fMRI acquisition of the 25 patients with diagnosis of MTLE who had interictal epileptiform discharges (IEDs) in the intra-MRI EEG: 13 MTLE-HS and 12 MTLE-NL. fMRI was performed using echo-planar images in a 3T MRI coupled with EEG acquired with 64 MRI-compatible electrodes. In the first level analyses, the time of the IEDs ipsilateral to the epileptogenic zone was used as the paradigm, and four contrasts maps were built according to the variation of the hemodynamic response function (HRF) peaks (0, +3, +5, and +7 s). Second level group analyses were performed combining the contrast maps of MTLE-HS or MTLE-NL patients with each different HRF obtained at the first level. Areas of gray matter atrophy were evaluated with voxel-based morphometry (VBM) in both groups. RESULTS: MTLE-HS and MTLE-NL had IED-related positive BOLD (posBOLD) detected in the ipsilateral anterior temporal lobe and insula. However, only MTLE-HS had significant posBOLD on contralateral hippocampus and anterior cingulate, whereas MTLE-NL had areas of posBOLD on ipsilateral frontal lobe. Both groups had significant IED-related negBOLD responses in areas of the default mode network (DMN), such as posterior cingulate and precuneus. There was no overlap of both posBOLD and negBOLD and areas of atrophy detected by VBM. SIGNIFICANCE: Similar IEDs have different patterns of hemodynamic responses in sub-groups of MTLE. In both MTLE-HS and MTLE-NL, there is a possible suppression of the DMN related to IEDs, as demonstrated by the negBOLD in these areas. The brain areas involved in the interictal related hemodynamic network are not the regions with the most significant gray matter atrophy in MTLE with or without MRI signs of HS.

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.

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

BACKGROUND: Mesial 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. RESULTS: We 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. CONCLUSIONS: The findings presented here suggest that left HS causes more reduction of functional connectivity than right HS in subjects with left hemisphere dominance for language.

Caffeine and Placebo Improved Maximal Exercise Performance Despite Unchanged Motor Cortex Activation and Greater Prefrontal Cortex Deoxygenation.

Caffeine (CAF) is an ergogenic aid used to improve exercise performance. Independent studies have suggested that caffeine may have the ability to increase corticospinal excitability, thereby decreasing the motor cortex activation required to generate a similar motor output. However, CAF has also been suggested to induce a prefrontal cortex (PFC) deoxygenation. Others have suggested that placebo (PLA) may trigger comparable effects to CAF, as independent studies found PLA effects on motor performance, corticospinal excitability, and PFC oxygenation. Thus, we investigated if CAF and CAF-perceived PLA may improve motor performance, despite the likely unchanged MC activation and greater PFC deoxygenation. Nine participants (26.4 ± 4.8 years old, VO2MAX of 42.2 ± 4.6 mL kg-1 min-1) performed three maximal incremental tests (MITs) in control (no supplementation) and ∼60 min after CAF and PLA ingestion. PFC oxygenation (near-infrared spectroscopy at Fp1 position), MC activation (EEG at Cz position) and vastus lateralis and rectus femoris muscle activity (EMG) were measured throughout the tests. Compared to control, CAF and PLA increased rectus femoris muscle EMG (P = 0.030; F = 2.88; d = 0.84) at 100% of the MIT, and enhanced the peak power output (P = 0.006; F = 12.97; d = 1.8) and time to exhaustion (P = 0.007; F = 12.97; d = 1.8). In contrast, CAF and PLA did not change MC activation, but increased the PFC deoxygenation as indicated by the lower O2Hb (P = 0.001; F = 4.68; d = 1.08) and THb concentrations (P = 0.01; F = 1.96; d = 0.7) at 80 and 100% the MIT duration. These results showed that CAF and CAF-perceived PLA had the ability to improve motor performance, despite unchanged MC activation and greater PFC deoxygenation. The effectiveness of CAF as ergogenic aid to improve MIT performance was challenged.

Cerebral Regulation in Different Maximal Aerobic Exercise Modes.

We investigated cerebral responses, simultaneously with peripheral and ratings of perceived exertion (RPE) responses, during different VO2MAX-matched aerobic exercise modes. Nine cyclists (VO2MAX of 57.5 ± 6.2 ml·kg(-1)·min(-1)) performed a maximal, controlled-pace incremental test (MIT) and a self-paced 4 km time trial (TT4km). Measures of cerebral (COX) and muscular (MOX) oxygenation were assessed throughout the exercises by changes in oxy- (O2Hb) and deoxy-hemoglobin (HHb) concentrations over the prefrontal cortex (PFC) and vastus lateralis (VL) muscle, respectively. Primary motor cortex (PMC) electroencephalography (EEG), VL, and rectus femoris EMG were also assessed throughout the trials, together with power output and cardiopulmonary responses. The RPE was obtained at regular intervals. Similar motor output (EMG and power output) occurred from 70% of the duration in MIT and TT4km, despite the greater motor output, muscle deoxygenation (↓ MOX) and cardiopulmonary responses in TT4km before that point. Regarding cerebral responses, there was a lower COX (↓ O2Hb concentrations in PFC) at 20, 30, 40, 50 and 60%, but greater at 100% of the TT4km duration when compared to MIT. The alpha wave EEG in PMC remained constant throughout the exercise modes, with greater values in TT4km. The RPE was maximal at the endpoint in both exercises, but it increased slower in TT4km than in MIT. Results showed that similar motor output and effort tolerance were attained at the closing stages of different VO2MAX-matched aerobic exercises, although the different disturbance until that point. Regardless of different COX responses during most of the exercises duration, activation in PMC was preserved throughout the exercises, suggesting that these responses may be part of a centrally-coordinated exercise regulation.

Investigation of NAA and NAAG dynamics underlying visual stimulation using MEGA-PRESS in a functional MRS experiment.

N-acetyl-aspartate (NAA) is responsible for the majority of the most prominent peak in (1)H-MR spectra, and has been used as diagnostic marker for several pathologies. However, ~10% of this peak can be attributed to N-acetyl-aspartyl-glutamate (NAAG), a neuropeptide whose release may be triggered by intense neuronal activation. Separate measurement of NAA and NAAG using MRS is difficult due to large superposition of their spectra. Specifically, in functional MRS (fMRS) experiments, most work has evaluated the sum NAA+NAAG, which does not appear to change during experiments. The aim of this work was to design and perform an fMRS experiment using visual stimulation and a spectral editing sequence, MEGA-PRESS, to further evaluate the individual dynamics of NAA and NAAG during brain activation. The functional paradigm used consisted of three blocks, starting with a rest (baseline) block of 320 s, followed by a stimulus block (640 s) and a rest block (640 s). Twenty healthy subjects participated in this study. On average, subjects followed a pattern of NAA decrease and NAAG increase during stimulation, with a tendency to return to basal levels at the end of the paradigm, with a peak NAA decrease of -(21±19)% and a peak NAAG increase of (64±62)% (Wilcoxon test, p<0.05). These results may relate to: 1) the only known NAAG synthesis pathway is from NAA and glutamate; 2) a relationship between NAAG and the BOLD response.