Improving fMRI in signal drop-out regions at 7 T by using tailored radio-frequency pulses: application to the ventral occipito-temporal cortex.

OBJECTIVE: Signal drop-off occurs in echo-planar imaging in inferior brain areas due to field gradients from susceptibility differences between air and tissue. Tailored-RF pulses based on a hyperbolic secant (HS) have been shown to partially recover signal at 3 T, but have not been tested at higher fields. MATERIALS AND METHODS: The aim of this study was to compare the performance of an optimized tailored-RF gradient-echo echo-planar imaging (TRF GRE-EPI) sequence with standard GRE-EPI at 7 T, in a passive viewing of faces or objects fMRI paradigm in healthy subjects. RESULTS: Increased temporal-SNR (tSNR) was observed in the middle and inferior temporal lobes and orbitofrontal cortex of all subjects scanned, but elsewhere tSNR decreased relative to the standard acquisition. In the TRF GRE-EPI, increased functional signal was observed in the fusiform, lateral occipital cortex, and occipital pole, regions known to be part of the visual pathway involved in face-object perception. CONCLUSION: This work highlights the potential of TRF approaches at 7 T. Paired with a reversed-gradient distortion correction to compensate for in-plane susceptibility gradients, it provides an improved acquisition strategy for future neurocognitive studies at ultra-high field imaging in areas suffering from static magnetic field inhomogeneities.

Memory network plasticity after temporal lobe resection: a longitudinal functional imaging study.

Anterior temporal lobe resection can control seizures in up to 80% of patients with temporal lobe epilepsy. Memory decrements are the main neurocognitive complication. Preoperative functional reorganization has been described in memory networks, but less is known of postoperative reorganization. We investigated reorganization of memory-encoding networks preoperatively and 3 and 12 months after surgery. We studied 36 patients with unilateral medial temporal lobe epilepsy (19 right) before and 3 and 12 months after anterior temporal lobe resection. Fifteen healthy control subjects were studied at three equivalent time points. All subjects had neuropsychological testing at each of the three time points. A functional magnetic resonance imaging memory-encoding paradigm of words and faces was performed with subsequent out-of-scanner recognition assessments. Changes in activations across the time points in each patient group were compared to changes in the control group in a single flexible factorial analysis. Postoperative change in memory across the time points was correlated with postoperative activations to investigate the efficiency of reorganized networks. Left temporal lobe epilepsy patients showed increased right anterior hippocampal and frontal activation at both 3 and 12 months after surgery relative to preoperatively, for word and face encoding, with a concomitant reduction in left frontal activation 12 months postoperatively. Right anterior hippocampal activation 12 months postoperatively correlated significantly with improved verbal learning in patients with left temporal lobe epilepsy from preoperatively to 12 months postoperatively. Preoperatively, there was significant left posterior hippocampal activation that was sustained 3 months postoperatively at word encoding, and increased at face encoding. For both word and face encoding this was significantly reduced from 3 to 12 months postoperatively. Patients with right temporal lobe epilepsy showed increased left anterior hippocampal activation on word encoding from 3 to 12 months postoperatively compared to preoperatively. On face encoding, left anterior hippocampal activations were present preoperatively and 12 months postoperatively. Left anterior hippocampal and orbitofrontal cortex activations correlated with improvements in both design and verbal learning 12 months postoperatively. On face encoding, there were significantly increased left posterior hippocampal activations that reduced significantly from 3 to 12 months postoperatively. Postoperative changes occur in the memory-encoding network in both left and right temporal lobe epilepsy patients across both verbal and visual domains. Three months after surgery, compensatory posterior hippocampal reorganization that occurs is transient and inefficient. Engagement of the contralateral hippocampus 12 months after surgery represented efficient reorganization in both patient groups, suggesting that the contralateral hippocampus contributes to memory outcome 12 months after surgery.

SAR prediction in adults and children by combining measured B1+ maps and simulations at 7.0 Tesla.

PURPOSE: To predict local and global specific absorption rate (SAR) in individual subjects. MATERIALS AND METHODS: SAR was simulated for a head volume coil for two imaging sequences: axial T1-weighted "zero" time-of-echo (ZTE) sequence, sagittal T2-weighted fluid attenuated inversion recovery (FLAIR). Two head models (one adult, one child) were simulated inside the coil. For 19 adults and 27 children, measured B1 (+) maps were acquired, and global (head) SAR estimated by the system was recorded. We performed t-test between the B1 (+) in models and human subjects. The B1 (+) maps of individual subjects were used to scale the SAR simulated on the models, to predict local and global (head) SAR. A phantom experiment was performed to validate SAR prediction, using a fiberoptic temperature probe to measure the temperature rise due to ZTE scanning. RESULTS: The normalized B1 (+) standard deviation in subjects was not significantly different from that of the models (P > 0.68 and P > 0.54). The rise in temperature generated in the phantom by ZTE was 0.3°C; from the heat equation it followed that the temperature-based measured SAR was 2.74 W/kg, while the predicted value was 3.1 W/kg. CONCLUSION: For ZTE and FLAIR, limits on maximum local and global SAR were met in all subjects, both adults and children. To enhance safety in adults and children with 7.0 Tesla MR systems, we suggest the possibility of using SAR prediction. J. MAGN. RESON. IMAGING 2016;44:1048-1055.

7T MRI in focal epilepsy with unrevealing conventional field strength imaging.

OBJECTIVE: To assess the diagnostic yield of 7T magnetic resonance imaging (MRI) in detecting and characterizing structural lesions in patients with intractable focal epilepsy and unrevealing conventional (1.5 or 3T) MRI. METHODS: We conducted an observational clinical imaging study on 21 patients (17 adults and 4 children) with intractable focal epilepsy, exhibiting clinical and electroencephalographic features consistent with a single seizure-onset zone (SOZ) and unrevealing conventional MRI. Patients were enrolled at two tertiary epilepsy surgery centers and imaged at 7T, including whole brain (three-dimensional [3D] T1 -weighted [T1W] fast-spoiled gradient echo (FSPGR), 3D susceptibility-weighted angiography [SWAN], 3D fluid-attenuated inversion recovery [FLAIR]) and targeted imaging (2D T2*-weighted dual-echo gradient-recalled echo [GRE] and 2D gray-white matter tissue border enhancement [TBE] fast spin echo inversion recovery [FSE-IR]). MRI studies at 1.5 or 3T deemed unrevealing at the referral center were reviewed by three experts in epilepsy imaging. Reviewers were provided information regarding the suspected localization of the SOZ. The same team subsequently reviewed 7T images. Agreement in imaging interpretation was reached through consensus-based discussions based on visual identification of structural abnormalities and their likely correlation with clinical and electrographic data. RESULTS: 7T MRI revealed structural lesions in 6 (29%) of 21 patients. The diagnostic gain in detection was obtained using GRE and FLAIR images. Four of the six patients with abnormal 7T underwent epilepsy surgery. Histopathology revealed focal cortical dysplasia (FCD) in all. In the remaining 15 patients (71%), 7T MRI remained unrevealing; 4 of the patients underwent epilepsy surgery and histopathologic evaluation revealed gliosis. SIGNIFICANCE: 7T MRI improves detection of epileptogenic FCD that is not visible at conventional field strengths. A dedicated protocol including whole brain FLAIR and GRE images at 7T targeted at the suspected SOZ increases the diagnostic yield.

Assessment of Silent T1-weighted head imaging at 7 T.

OBJECTIVES: This study aimed to assess the performance of a "Silent" zero time of echo (ZTE) sequence for T1-weighted brain imaging using a 7 T MRI system. METHODS: The Silent sequence was evaluated qualitatively by two neuroradiologists, as well as quantitatively in terms of tissue contrast, homogeneity, signal-to-noise ratio (SNR) and acoustic noise. It was compared to conventional T1-weighted imaging (FSPGR). Adequacy for automated segmentation was evaluated in comparison with FSPGR acquired at 7 T and 1.5 T. Specific absorption rate (SAR) was also measured. RESULTS: Tissue contrast and homogeneity in Silent were remarkable in deep brain structures and in the occipital and temporal lobes. Mean tissue contrast was significantly (p < 0.002) higher in Silent (0.25) than in FSPGR (0.11), which favoured automated tissue segmentation. On the other hand, Silent images had lower SNR with respect to conventional imaging: average SNR of FSPGR was 2.66 times that of Silent. Silent images were affected by artefacts related to projection reconstruction, which nevertheless did not compromise the depiction of brain tissues. Silent acquisition was 35 dB(A) quieter than FSPGR and less than 2.5 dB(A) louder than ambient noise. Six-minute average SAR was <2 W/kg. CONCLUSIONS: The ZTE Silent sequence provides high-contrast T1-weighted imaging with low acoustic noise at 7 T. KEY POINTS: • "Silent" is an MRI technique allowing zero time of echo acquisition • Its feasibility and performance were assessed on a 7 T MRI system • Image quality in several regions was higher than in conventional techniques • Imaging acoustic noise was dramatically reduced compared with conventional imaging • "Silent" is suitable for T1-weighted head imaging at 7 T.

Motor co-activation in siblings of patients with juvenile myoclonic epilepsy: an imaging endophenotype?

Juvenile myoclonic epilepsy is a heritable idiopathic generalized epilepsy syndrome, characterized by myoclonic jerks and frequently triggered by cognitive effort. Impairment of frontal lobe cognitive functions has been reported in patients with juvenile myoclonic epilepsy and their unaffected siblings. In a recent functional magnetic resonance imaging study we reported abnormal co-activation of the motor cortex and increased functional connectivity between the motor system and prefrontal cognitive networks during a working memory paradigm, providing an underlying mechanism for cognitively triggered jerks. In this study, we used the same task in 15 unaffected siblings (10 female; age range 18-65 years, median 40) of 11 of those patients with juvenile myoclonic epilepsy (six female; age range 22-54 years, median 35) and compared functional magnetic resonance imaging activations with 20 age- and gender-matched healthy control subjects (12 female; age range 23-46 years, median 30.5). Unaffected siblings showed abnormal primary motor cortex and supplementary motor area co-activation with increasing cognitive load, as well as increased task-related functional connectivity between motor and prefrontal cognitive networks, with a similar pattern to patients (P < 0.001 uncorrected; 20-voxel threshold extent). This finding in unaffected siblings suggests that altered motor system activation and functional connectivity is not medication- or seizure-related, but represents a potential underlying mechanism for impairment of frontal lobe functions in both patients and siblings, and so constitutes an endophenotype of juvenile myoclonic epilepsy.

Working memory network plasticity after anterior temporal lobe resection: a longitudinal functional magnetic resonance imaging study.

Working memory is a crucial cognitive function that is disrupted in temporal lobe epilepsy. It is unclear whether this impairment is a consequence of temporal lobe involvement in working memory processes or due to seizure spread to extratemporal eloquent cortex. Anterior temporal lobe resection controls seizures in 50-80% of patients with drug-resistant temporal lobe epilepsy and the effect of surgery on working memory are poorly understood both at a behavioural and neural level. We investigated the impact of temporal lobe resection on the efficiency and functional anatomy of working memory networks. We studied 33 patients with unilateral medial temporal lobe epilepsy (16 left) before, 3 and 12 months after anterior temporal lobe resection. Fifteen healthy control subjects were also assessed in parallel. All subjects had neuropsychological testing and performed a visuospatial working memory functional magnetic resonance imaging paradigm on these three separate occasions. Changes in activation and deactivation patterns were modelled individually and compared between groups. Changes in task performance were included as regressors of interest to assess the efficiency of changes in the networks. Left and right temporal lobe epilepsy patients were impaired on preoperative measures of working memory compared to controls. Working memory performance did not decline following left or right temporal lobe resection, but improved at 3 and 12 months following left and, to a lesser extent, following right anterior temporal lobe resection. After left anterior temporal lobe resection, improved performance correlated with greater deactivation of the left hippocampal remnant and the contralateral right hippocampus. There was a failure of increased deactivation of the left hippocampal remnant at 3 months after left temporal lobe resection compared to control subjects, which had normalized 12 months after surgery. Following right anterior temporal lobe resection there was a progressive increase of activation in the right superior parietal lobe at 3 and 12 months after surgery. There was greater deactivation of the right hippocampal remnant compared to controls between 3 and 12 months after right anterior temporal lobe resection that was associated with lesser improvement in task performance. Working memory improved after anterior temporal lobe resection, particularly following left-sided resections. Postoperative working memory was reliant on the functional capacity of the hippocampal remnant and, following left resections, the functional reserve of the right hippocampus. These data suggest that working memory following temporal lobe resection is dependent on the engagement of the posterior medial temporal lobes and eloquent cortex.

Investigation of maximum local specific absorption rate in 7 T magnetic resonance with respect to load size by use of electromagnetic simulations.

Local specific absorption rate (SAR) evaluation in ultra high field (UHF) magnetic resonance (MR) systems is a major concern. In fact, at UHF, radiofrequency (RF) field inhomogeneity generates hot-spots that could cause localized tissue heating. Unfortunately, local SAR measurements are not available in present MR systems; thus, electromagnetic simulations must be performed for RF fields and SAR analysis. In this study, we used three-dimensional full-wave numerical electromagnetic simulations to investigate the dependence of local SAR at 7.0 T with respect to subject size in two different scenarios: surface coil loaded by adult and child calves and quadrature volume coil loaded by adult and child heads. In the surface coil scenario, maximum local SAR decreased with decreasing load size, provided that the RF magnetic fields for the different load sizes were scaled to achieve the same slice average value. On the contrary, in the volume coil scenario, maximum local SAR was up to 15% higher in children than in adults.

Language dominance assessment in a bilingual population: validity of fMRI in the second language.

OBJECTIVE: Assessment of language dominance using functional magnetic resonance imaging (fMRI) is a standard tool to estimate the risk of language function decline after epilepsy surgery. Although there has been considerable research in the characterization of language networks in bilingual individuals; little is known about the clinical usefulness of language mapping in a secondary language in patients with epilepsy, and how language lateralization assessed by fMRI may differ by the use of native or a secondary language paradigms. In this study we investigate language representation in a population of nonnative English speakers to assess differences in fMRI language lateralization between the first (native) and second language (English). METHODS: Sixteen nonnative English-speaking patients with focal drug-resistant epilepsy underwent language fMRI in their first (native) language (L1) and in English (L2). Differences between language maps using L1 and L2 paradigms were examined at the single subject level by comparing within-subject lateralization indexes obtained for each language. Differences at the group level were examined for each of the tasks and languages. RESULTS: Group maps for the second language (English) showed overlapping areas of activation with the native language, but with larger clusters, and more bilaterally distributed than for the first language. However, at the individual level, lateralization indexes were concordant between the two languages, except for one patient with bilateral hippocampal sclerosis who was left dominant in English and showed bilateral dominance for verb generation and right dominance for verbal fluency in his native tongue. SIGNIFICANCE: Language lateralization can generally be reliably derived from fMRI tasks in a second language provided that the subject can follow the task. Subjects with greater likelihood of atypical language representation should be evaluated more carefully, using more than one language paradigm.

A functional magnetic resonance imaging study mapping the episodic memory encoding network in temporal lobe epilepsy.

Functional magnetic resonance imaging has demonstrated reorganization of memory encoding networks within the temporal lobe in temporal lobe epilepsy, but little is known of the extra-temporal networks in these patients. We investigated the temporal and extra-temporal reorganization of memory encoding networks in refractory temporal lobe epilepsy and the neural correlates of successful subsequent memory formation. We studied 44 patients with unilateral temporal lobe epilepsy and hippocampal sclerosis (24 left) and 26 healthy control subjects. All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words with subsequent out-of-scanner recognition assessments. A blocked analysis was used to investigate activations during encoding and neural correlates of subsequent memory were investigated using an event-related analysis. Event-related activations were then correlated with out-of-scanner verbal and visual memory scores. During word encoding, control subjects activated the left prefrontal cortex and left hippocampus whereas patients with left hippocampal sclerosis showed significant additional right temporal and extra-temporal activations. Control subjects displayed subsequent verbal memory effects within left parahippocampal gyrus, left orbitofrontal cortex and fusiform gyrus whereas patients with left hippocampal sclerosis activated only right posterior hippocampus, parahippocampus and fusiform gyrus. Correlational analysis showed that patients with left hippocampal sclerosis with better verbal memory additionally activated left orbitofrontal cortex, anterior cingulate cortex and left posterior hippocampus. During face encoding, control subjects showed right lateralized prefrontal cortex and bilateral hippocampal activations. Patients with right hippocampal sclerosis showed increased temporal activations within the superior temporal gyri bilaterally and no increased extra-temporal areas of activation compared with control subjects. Control subjects showed subsequent visual memory effects within right amygdala, hippocampus, fusiform gyrus and orbitofrontal cortex. Patients with right hippocampal sclerosis showed subsequent visual memory effects within right posterior hippocampus, parahippocampal and fusiform gyri, and predominantly left hemisphere extra-temporal activations within the insula and orbitofrontal cortex. Correlational analysis showed that patients with right hippocampal sclerosis with better visual memory activated the amygdala bilaterally, right anterior parahippocampal gyrus and left insula. Right sided extra-temporal areas of reorganization observed in patients with left hippocampal sclerosis during word encoding and bilateral lateral temporal reorganization in patients with right hippocampal sclerosis during face encoding were not associated with subsequent memory formation. Reorganization within the medial temporal lobe, however, is an efficient process. The orbitofrontal cortex is critical to subsequent memory formation in control subjects and patients. Activations within anterior cingulum and insula correlated with better verbal and visual subsequent memory in patients with left and right hippocampal sclerosis, respectively, representing effective extra-temporal recruitment.

Memory reorganization following anterior temporal lobe resection: a longitudinal functional MRI study.

Anterior temporal lobe resection controls seizures in 50-60% of patients with intractable temporal lobe epilepsy but may impair memory function, typically verbal memory following left, and visual memory following right anterior temporal lobe resection. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated the reorganization of memory function in patients with temporal lobe epilepsy before and after left or right anterior temporal lobe resection and the efficiency of postoperative memory networks. We studied 46 patients with unilateral medial temporal lobe epilepsy (25/26 left hippocampal sclerosis, 16/20 right hippocampal sclerosis) before and after anterior temporal lobe resection on a 3 T General Electric magnetic resonance imaging scanner. All subjects had neuropsychological testing and performed a functional magnetic resonance imaging memory encoding paradigm for words, pictures and faces, testing verbal and visual memory in a single scanning session, preoperatively and again 4 months after surgery. Event-related analysis revealed that patients with left temporal lobe epilepsy had greater activation in the left posterior medial temporal lobe when successfully encoding words postoperatively than preoperatively. Greater pre- than postoperative activation in the ipsilateral posterior medial temporal lobe for encoding words correlated with better verbal memory outcome after left anterior temporal lobe resection. In contrast, greater postoperative than preoperative activation in the ipsilateral posterior medial temporal lobe correlated with worse postoperative verbal memory performance. These postoperative effects were not observed for visual memory function after right anterior temporal lobe resection. Our findings provide evidence for effective preoperative reorganization of verbal memory function to the ipsilateral posterior medial temporal lobe due to the underlying disease, suggesting that it is the capacity of the posterior remnant of the ipsilateral hippocampus rather than the functional reserve of the contralateral hippocampus that is important for maintaining verbal memory function after anterior temporal lobe resection. Early postoperative reorganization to ipsilateral posterior or contralateral medial temporal lobe structures does not underpin better performance. Additionally our results suggest that visual memory function in right temporal lobe epilepsy is affected differently by right anterior temporal lobe resection than verbal memory in left temporal lobe epilepsy.

Tissue Border Enhancement by inversion recovery MRI at 7.0 Tesla.

INTRODUCTION: This contribution presents a magnetic resonance imaging (MRI) acquisition technique named Tissue Border Enhancement (TBE), whose purpose is to produce images with enhanced visualization of borders between two tissues of interest without any post-processing. METHODS: The technique is based on an inversion recovery sequence that employs an appropriate inversion time to produce images where the interface between two tissues of interest is hypo-intense; therefore, tissue borders are clearly represented by dark lines. This effect is achieved by setting imaging parameters such that two neighboring tissues of interest have magnetization with equal magnitude but opposite sign; therefore, the voxels containing a mixture of each tissue (that is, the tissue interface) possess minimal net signal. The technique was implemented on a 7.0 T MRI system. RESULTS: This approach can assist the definition of tissue borders, such as that between cortical gray matter and white matter; therefore, it could facilitate segmentation procedures, which are often challenging on ultra-high-field systems due to inhomogeneous radiofrequency distribution. TBE allows delineating the contours of structural abnormalities, and its capabilities were demonstrated with patients with focal cortical dysplasia, gray matter heterotopia, and polymicrogyria. CONCLUSION: This technique provides a new type of image contrast and has several possible applications in basic neuroscience, neurogenetic research, and clinical practice, as it could improve the detection power of MRI in the characterization of cortical malformations, enhance the contour of small anatomical structures of interest, and facilitate cortical segmentation.

Optic radiation tractography and vision in anterior temporal lobe resection.

OBJECTIVE: Anterior temporal lobe resection (ATLR) is an effective treatment for refractory temporal lobe epilepsy but may result in a contralateral superior visual field deficit (VFD) that precludes driving in the seizure-free patient. Diffusion tensor imaging (DTI) tractography can delineate the optic radiation preoperatively and stratify risk. It would be advantageous to incorporate display of tracts into interventional magnetic resonance imaging (MRI) to guide surgery. METHODS: We studied 20 patients undergoing ATLR. Structural MRI scans, DTI, and visual fields were acquired before and 3 to 12 months following surgery. Tractography of the optic radiation was performed on preoperative images and propagated onto postoperative images. The anteroposterior extent of the damage to Meyer's loop was determined, and visual loss was quantified using Goldmann perimetry. RESULTS: Twelve patients (60%) suffered a VFD (10-92% of upper quadrant; median, 39%). Image registration took <3 minutes and predicted that Meyer's loop was 4.4 to 18.7mm anterior to the resection margin in these patients, but 0.0 to 17.6mm behind the resection margin in the 8 patients without VFD. The extent of damage to Meyer's loop significantly correlated with the degree of VFD and explained 65% of the variance in this measure. INTERPRETATION: The optic radiation can be accurately delineated by tractography and propagated onto postoperative images. The technique is fast enough to propagate accurate preoperative tractography onto intraoperative scans acquired during neurosurgery, with the potential to reduce the risk of VFD.

Structural correlates of impaired working memory in hippocampal sclerosis.

PURPOSE: Temporal lobe epilepsy (TLE) has been considered to impair long-term memory, whilst not affecting working memory, but recent evidence suggests that working memory is compromised. Functional MRI (fMRI) studies demonstrate that working memory involves a bilateral frontoparietal network the activation of which is disrupted in hippocampal sclerosis (HS). A specific role of the hippocampus to deactivate during working memory has been proposed with this mechanism faulty in patients with HS. Structural correlates of disrupted working memory in HS have not been explored. METHODS: We studied 54 individuals with medically refractory TLE and unilateral HS (29 left) and 28 healthy controls. Subjects underwent 3T structural MRI, a visuospatial n-back fMRI paradigm and diffusion tensor imaging (DTI). Working memory capacity assessed by three span tasks (digit span backwards, gesture span, motor sequences) was combined with performance in the visuospatial paradigm to give a global working memory measure. Gray and white matter changes were investigated using voxel-based morphometry and voxel-based analysis of DTI, respectively. KEY FINDINGS: Individuals with left or right HS performed less well than healthy controls on all measures of working memory. fMRI demonstrated a bilateral frontoparietal network during the working memory task with reduced activation of the right parietal lobe in both patient groups. In left HS, gray matter loss was seen in the ipsilateral hippocampus and parietal lobe, with maintenance of the gray matter volume of the contralateral parietal lobe associated with better performance. White matter integrity within the frontoparietal network, in particular the superior longitudinal fasciculus and cingulum, and the contralateral temporal lobe, was associated with working memory performance. In right HS, gray matter loss was also seen in the ipsilateral hippocampus and parietal lobe. Working memory performance correlated with the gray matter volume of both frontal lobes and white matter integrity within the frontoparietal network and contralateral temporal lobe. SIGNIFICANCE: Our data provide further evidence that working memory is disrupted in HS and impaired integrity of both gray and white matter is seen in functionally relevant areas. We suggest this forms the structural basis of the impairment of working memory, indicating widespread and functionally significant structural changes in patients with apparently isolated HS.

Risk-taking behavior in juvenile myoclonic epilepsy.

OBJECTIVE: Patients with juvenile myoclonic epilepsy (JME) often present with risk-taking behavior, suggestive of frontal lobe dysfunction. Recent studies confirm functional and microstructural changes within the frontal lobes in JME. This study aimed at characterizing decision-making behavior in JME and its neuronal correlates using functional magnetic resonance imaging (fMRI). METHODS: We investigated impulsivity in 21 JME patients and 11 controls using the Iowa Gambling Task (IGT), which measures decision making under ambiguity. Performance on the IGT was correlated with activation patterns during an fMRI working memory task. RESULTS: Both patients and controls learned throughout the task. Post hoc analysis revealed a greater proportion of patients with seizures than seizure-free patients having difficulties in advantageous decision making, but no difference in performance between seizure-free patients and controls. Functional imaging of working memory networks showed that overall poor IGT performance was associated with an increased activation in the dorsolateral prefrontal cortex (DLPFC) in JME patients. Impaired learning during the task and ongoing seizures were associated with bilateral medial prefrontal cortex (PFC) and presupplementary motor area, right superior frontal gyrus, and left DLPFC activation. SIGNIFICANCE: Our study provides evidence that patients with JME and ongoing seizures learn significantly less from previous experience. Interictal dysfunction within "normal" working memory networks, specifically, within the DLPFC and medial PFC structures, may affect their ability to learn.

Abnormal thalamocortical structural and functional connectivity in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy is the most common idiopathic generalized epilepsy, characterized by frequent myoclonic jerks, generalized tonic-clonic seizures and, less commonly, absences. Neuropsychological and, less consistently, anatomical studies have indicated frontal lobe dysfunction in the disease. Given its presumed thalamo-cortical basis, we investigated thalamo-cortical structural connectivity, as measured by diffusion tensor imaging, in a cohort of 28 participants with juvenile myoclonic epilepsy and detected changes in an anterior thalamo-cortical bundle compared with healthy control subjects. We then investigated task-modulated functional connectivity from the anterior thalamic region identified using functional magnetic resonance imaging in a task consistently shown to be impaired in this group, phonemic verbal fluency. We demonstrate an alteration in task-modulated connectivity in a region of frontal cortex directly connected to the thalamus via the same anatomical bundle, and overlapping with the supplementary motor area. Further, we show that the degree of abnormal connectivity is related to disease severity in those with active seizures. By integrating methods examining structural and effective interregional connectivity, these results provide convincing evidence for abnormalities in a specific thalamo-cortical circuit, with reduced structural and task-induced functional connectivity, which may underlie the functional abnormalities in this idiopathic epilepsy.

Automated MR image classification in temporal lobe epilepsy.

In those with drug refractory focal epilepsy, MR imaging is important for identifying structural causes of seizures that may be amenable to surgical treatment. In up to 25% of potential surgical candidates, however, MRI is reported as unremarkable even when employing epilepsy specific sequences. Automated MRI classification is a desirable tool to augment the interpretation of images, especially when changes are subtle or distributed and may be missed on visual inspection. Support vector machines (SVM) have recently been described to be useful for voxel-based MR image classification. In the present study we sought to evaluate whether this method is feasible in temporal lobe epilepsy, with adequate accuracy. We studied 38 patients with hippocampal sclerosis and unilateral (mesial) temporal lobe epilepsy (mTLE) (20 left) undergoing presurgical evaluation and 22 neurologically normal control subjects. 3D T1-weighted images were acquired at 3T (GE Excite), segmented into tissue classes, normalized and smoothed with SPM8. Diffusion tensor imaging (DTI) and double echo images for T2 relaxometry were also acquired and processed. The SVM analysis was done with the libsvm software package in a leave-one-out cross-validation design and predictive accuracy was measured. Local weighting was applied by SPM F-contrast maps. Best accuracies were achieved using the gray matter based segmentation (90-100%) and mean diffusivity (95-97%). For the three-way classification, accuracies were 88 and 93% respectively. Local weighting generally improved the accuracies except in the FA-based processing for which no effect was noted. Removing the hippocampus from the analysis, on the other hand, reduced the obtainable diagnostic indices but these were still >90% for DTI-based methods and lateralization based on gray matter maps. These findings show that automated SVM image classification can achieve high diagnostic accuracy in mTLE and that voxel-based MRI can be used at the individual subject level. This could be helpful for screening assessments of MRI scans in patients with epilepsy and when no lesion is detected on visual evaluation.

The effect of local perturbation fields on human DTI: characterisation, measurement and correction.

Indices derived from diffusion tensor imaging (DTI) data, including the mean diffusivity (MD) and fractional anisotropy (FA), are often used to better understand the microstructure of the brain. DTI, however, is susceptible to imaging artefacts, which can bias these indices. The most important sources of artefacts in DTI include eddy currents, nonuniformity and mis-calibration of gradients. We modelled these and other artefacts using a local perturbation field (LPF) approach. LPFs during the diffusion-weighting period describe the local mismatches between the effective and the expected diffusion gradients resulting in a spatially varying error in the diffusion weighting B matrix and diffusion tensor estimation. We introduced a model that makes use of phantom measurements to provide a robust estimation of the LPF in DTI without requiring any scanner-hardware-specific information or special MRI sequences. We derived an approximation of the perturbed diffusion tensor in the isotropic-diffusion limit that can be used to identify regions in any DTI index map that are affected by LPFs. Using these models, we simulated and measured LPFs and characterised their effect on human DTI for three different clinical scanners. The small FA values found in grey matter were biased towards greater anisotropy leading to lower grey-to-white matter contrast (up to 10%). Differences in head position due to e.g. repositioning produced errors of up to 10% in the MD, reducing comparability in multi-centre or longitudinal studies. We demonstrate the importance of the proposed correction by showing improved consistency across scanners, different head positions and an increased FA contrast between grey and white matter.

Cortical abnormalities and their cognitive correlates in patients with temporal lobe epilepsy and interictal psychosis.

PURPOSE: To determine whether cortical abnormalities are more severe and widespread in patients with temporal lobe epilepsy (TLE) and interictal psychosis (IP) compared to those with TLE only (NIP) and healthy controls (HC), and to explore the associations between cortical parameters (area, thickness and volume), psychotic symptoms, and cognitive performance. METHODS: Twenty-two patients with IP (9 male; 10 hippocampal sclerosis, HS), 23 TLE nonpsychotic (NIP) patients (11 male; 13 HS) matched for duration of epilepsy and 20 HC participated. Surface-based morphometry (SBM) was used to measure cortical parameters. Cognition was examined in IP and NIP patients. Associations between cortical parameters and cognition were examined using linear mixed models adjusted by age, gender, and brain volume. KEY FINDINGS: IP patients had an earlier onset of epilepsy, more status epilepticus, and worse cognitive performance than NIP patients. In IP patients, cortical thickness was reduced in the inferior frontal gyrus (IFG), and their current IQ was associated with decreases in area, but not thickness, in regions of the frontotemporal cortex. SIGNIFICANCE: IP likely reflects the interplay of psychosis-related genetic factors and the cumulative effects of seizure activity on the brain. Cortical thinning in the IFG, a region implicated in schizophrenia, is likely to be related to seizure activity, whereas changes in IQ, associated with reductions in area of frontotemporal cortex, may be related to the presence of psychosis.

Memory in frontal lobe epilepsy: an fMRI study.

PURPOSE: Focal epilepsies are often associated with structural and functional changes that may extend beyond the area of seizure onset. In this study we investigated the functional anatomy of memory in patients with frontal lobe epilepsy (FLE), focusing on the local and remote effects of FLE on the networks supporting memory encoding. METHODS: We studied 32 patients with drug-resistant FLE and 18 controls using a functional magnetic resonance imaging (fMRI) memory encoding paradigm. KEY FINDINGS: During encoding of stimuli, patients with FLE recruited more widely distributed areas than healthy controls, in particular within the frontal lobe contralateral to the seizure onset. Normal memory performance was associated with increased recruitment of frontal areas, and conversely a poor performance was associated with an absence of this increased recruitment and decreased activation in mesial temporal lobe areas. SIGNIFICANCE: In patients with FLE, recruitment of wider areas, particularly in the contralateral frontal lobe, appears to be an effective compensatory mechanism to maintain memory function. Impaired hippocampal activation is relatively rare and, in turn, associated with poor recognition memory.