Mesial Temporal Activity Research Articles

A clinically applicable functional MRI memory paradigm for use with pediatric patients

ObjectiveClinically employable functional MRI (fMRI) memory paradigms are not yet established for pediatric patient epilepsy surgery workups. Seeking to establish such a paradigm, we evaluated the effectiveness of memory fMRI tasks we developed by quantifying individual activation in a clinical pediatric setting, analyzing patterns of activation relative to the side of temporal lobe (TL) pathology, and comparing fMRI and Wada test results. MethodsWe retrospectively identified 72 patients aged 6.7–20.9 years with pathology (seizure focus and/or tumor) limited to the TL who had attempted memory and language fMRI tasks over a 9-year period as part of presurgical workups. Memory fMRI tasks required visualization of autobiographical memories in a block design alternating with covert counting. Language fMRI protocols involved verb and sentence generation. Scans were both qualitatively interpreted and quantitatively assessed for blood oxygenation level dependent (BOLD) signal change using region of interest (ROI) masks. We calculated the percentage of successfully scanned individual cases, compared 2 memory task activation masks in cases with left versus right TL pathology, and compared fMRI with Wada tests when available. Patients who had viable fMRI and Wada tests had generally concordant results. ResultsOf the 72 cases, 60 (83%), aged 7.6–20.9 years, successfully performed the memory fMRI tasks and 12 (17%) failed. Eleven of 12 unsuccessful scans were due to motion and/or inability to perform the tasks, and the success of a twelfth was indeterminate due to orthodontic metal artifact. Seven of the successful 60 cases had distorted anatomy that precluded employing predetermined masks for quantitative analysis. Successful fMRI memory studies showed bilateral mesial temporal activation and quantitatively demonstrated: (1) left activation (L-ACT) less than right activation (R-ACT) in cases with left temporal lobe (L-TL) pathology, (2) nonsignificant R-ACT less than L-ACT in cases with right temporal lobe (R-TL) pathology, and (3) lower L-ACT plus R-ACT activation for cases with L-TL versus R-TL pathology. Patients who had viable fMRI and Wada tests had generally concordant results. SignificanceThis study demonstrates evidence of an fMRI memory task paradigm that elicits reliable activation at the individual level and can generally be accomplished in clinically involved pediatric patients. This autobiographical memory paradigm showed activation in mesial TL structures, and cases with left compared to right TL pathology showed differences in activation consistent with extant literature in TL epilepsy. Further studies will be required to assess outcome prediction.

Establishing a Developmentally Appropriate fMRI Paradigm Relevant to Presurgical Mapping of Memory in Children

Functional magnetic resonance imaging (fMRI) is an established eloquent cortex mapping technique that is now an integral part of the pre-operative work-up in candidates for epilepsy surgery. Emerging evidence in adults with epilepsy suggests that material-specific fMRI paradigms can predict postoperative memory outcomes, however these paradigms are not suitable for children. In pediatric age, the use of memory fMRI paradigms designed for adults is complicated by the effect of developmental stages in cognitive maturation, the impairment experienced by some people with temporal lobe epilepsy (TLE) and the normal representation of memory function during development, which may differ from adults. We present a memory fMRI paradigm designed to activate mesial temporal lobe structures that is brief, independent of reading ability, and therefore a novel candidate for use in children. Data from 33 adults and 19 children (all healthy controls) show that the paradigm captures the expected leftward asymmetry of mesial temporal activation in adults. A more symmetrical pattern was observed in children, consistent with the progressive emergence of hemispheric specialisation across childhood. These data have important implications for the interpretation of presurgical memory fMRI in the pediatric setting. They also highlight the need to carefully consider the impact of cognitive development on fMRI tools used in clinical practice.

Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer's disease

We directly assessed mesial temporal activity in two Alzheimer’s disease (AD) patients without a history or EEG evidence of seizures, using intracranial foramen ovale electrodes. We detected clinically silent hippocampal seizures and epileptiform spikes during sleep, a period when both were most likely to interfere with memory consolidation. These index cases support a model in which early development of occult hippocampal hyperexcitability may contribute to the pathogenesis of AD.

Temporal lobe spikes: EEG-fMRI contributions to the "mesial vs. lateral" debate.

It has been reported that interictal epileptic discharges (IEDs) recorded in temporal regions on scalp EEG are unlikely to originate from mesial temporal structures. However, EEG-fMRI sometimes show mesial temporal activation. We hypothesized that BOLD activation in the temporal neocortex is weaker than in the mesial structures, reflecting the fact that propagated activity has less metabolic demand than the original discharge. Twelve patients with epilepsy who have BOLD response in mesial temporal structures were selected from our EEG-fMRI database. We searched the temporal lobe ipsilateral to IEDs and checked whether there is positive BOLD response in the neocortex. All IED types showed a BOLD response in the temporal neocortex ipsilateral to the mesial temporal BOLD response. T-values were higher in mesial temporal structures than in neocortex in 13/16 cases. Hemodynamic changes were observed in the mesial temporal lobe at the time of IEDs recorded from the temporal region on the scalp. The finding of smaller BOLD changes in the ipsilateral neocortex is in agreement with our hypothesis. Our study indicates that scalp-recorded temporal lobe spikes are likely to result from mesial temporal spikes propagating neuronally to the neocortex.

Changes in frontal-parietal activation and math skills performance following adaptive number sense training: Preliminary results from a pilot study

Number sense is believed to be critical for math development. It is putatively an implicitly learned skill and may therefore have limitations in terms of being explicitly trained, particularly in individuals with altered neurodevelopment. A case series study was conducted using an adaptive, computerised programme that focused on number sense and general problem-solving skills. The study was designed to investigate training effects on performance as well as brain function in a group of children with Turner syndrome who are at risk for math difficulties and altered development of math-related brain networks. Standardised measurements of math and math-related cognitive skills as well as functional magnetic resonance imaging (fMRI) were used to assess behavioural and neurobiological outcomes following training. Participants demonstrated significantly increased basic math skills, including number sense, and calculation as well as processing speed, cognitive flexibility and visual-spatial processing skills. With the exception of calculation, increased scores also were clinically significant (i.e., recovered) based on reliable change analysis. Participants additionally demonstrated significantly increased bilateral parietal lobe activation and decreased frontal-striatal and mesial temporal activation following the training programme. These findings show proof of concept for an accessible training approach that may be potentially associated with improved number sense, math and related skills, as well as functional changes in math-related neural systems, even among individuals at risk for altered brain development.

Left Mesial Temporal Sclerosis and Verbal Memory: A Magnetoencephalography Study

The purpose of this study is to examine the pattern of mesial temporal lobe activity in patients with left mesial temporal sclerosis (LMTS) and normal control subjects during a verbal memory task using magnetoencephalography. Six LMTS patients and seven normal control subjects performed a word recognition task while event-related neuromagnetic responses were recorded for 248 trials in each of two runs. An equivalent current dipole model was used to localize activity sources and determine if the right or left mesial temporal lobe was active. All six (100%) LMTS patients but only two (28%) normal control subjects had right mesial temporal activity (P < 0.02). Two (33%) LMTS patients and 6 (86%) normal control subjects had left mesial temporal activity (P = 0.27). No significant differences in latency or duration of activity were seen between left and right sides or between groups. Our data suggest that patients with left hippocampal dysfunction are more likely to recruit the right mesial temporal lobe during verbal memory tasks than normal control subjects. A trend toward less left mesial temporal activity in LMTS patients is seen as well. Further study is needed to determine the predictive value of this technique regarding postresection memory outcome.

Cluster analysis detection of functional MRI activity in temporal lobe epilepsy

The objective of this pilot study was to evaluate the ability of a novel method of cluster analysis, 2dTCA, for identifying and characterizing peak fluctuations in fMRI BOLD signals in the temporal lobes and the default-mode network in temporal lobe epilepsy (TLE) without EEG. BOLD fMRI images were acquired in 17 TLE patients and compared to EEG. The timing of significant transient BOLD peaks was estimated by 2dTCA, and activation maps were determined. Sixteen subjects (94%) showed apparent temporal lobe activation. Mesial temporal activation was present in 76.4% (13 patients). Temporal lobe or insula activations were detected ipsilateral to the EEG focus in 64.7% (11 patients), bilaterally with no predominance in 29.4% (5 patients), and exclusively contralateral to the EEG focus in none. Eleven subjects showed activation in the so-called default-mode network including posterior cingulate, bilateral posterior parietal cortex, and sometimes anterior cingulate cortex. These results demonstrate significant positive BOLD fluctuations in the temporal lobes and default-mode regions in a higher percentage of TLE patients than previously reported using other methods. These fluctuations appear physiologically relevant and suggest increased neural activity which may not be detected on scalp EEG, but which may be important in understanding the mechanisms and origins of epileptic discharges.

Functional MRI lateralization of memory in temporal lobe epilepsy

To determine the feasibility of using functional magnetic resonance imaging (fMRI) to detect asymmetries in the lateralization of memory activation in patients with temporal lobe epilepsy (TLE). Assessment of mesial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. fMRI offers several potential advantages over the current gold standard, intracarotid amobarbital testing (IAT). fMRI has already been successfully applied to language lateralization in TLE. fMRI was carried out in eight normal subjects and 10 consecutively recruited patients with TLE undergoing preoperative evaluation for epilepsy surgery. A complex visual scene encoding task known to activate mesial temporal structures was used during fMRI. Asymmetry ratios for mesial temporal activation were calculated, using regions of interest defined in normals. Patient findings were compared with the results of IAT performed as part of routine clinical evaluation. Task activation was nearly symmetric in normal subjects, whereas in patients with TLE, significant asymmetries were observed. In all nine patients in whom the IAT result was interpretable, memory asymmetry by fMRI concurred with the findings of IAT including two patients with paradoxical IAT memory lateralization ipsilateral to seizure focus. fMRI can be used to detect asymmetries in memory activation in patients with TLE. Because fMRI studies are noninvasive and provide excellent spatial resolution for functional activation, these preliminary results suggest a promising role for fMRI in improving the preoperative evaluation for epilepsy surgery.