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Biomedical subjects

D R Fish

Publications and source records attributed to D R Fish.

At least 19 recordsLinked to original sources

fMRI temporal clustering analysis in patients with frequent interictal epileptiform discharges: comparison with EEG-driven analysis.

Temporal clustering analysis (TCA) is an exploratory data-driven technique that has been proposed for the analysis of resting fMRI to localise epileptiform activity without need for simultaneous EEG. Conventionally, fMRI of epileptic activity has been limited to those patients with subtle clinical events or frequent interictal epileptiform EEG discharges, requiring simultaneous EEG recording, from which a linear model is derived to make valid statistical inferences from the fMRI data. We sought to evaluate TCA by comparing the results with those of EEG correlated fMRI in eight selected cases. Cases were selected with clear epileptogenic localisation or lateralisation on the basis of concordant EEG and structural MRI findings, in addition to concordant activations seen on EEG-derived fMRI analyses. In three, areas of activation were seen with TCA but none corresponding to the electro-clinical localisation or activations obtained with EEG driven analysis. Temporal clusters were closely coincident with times of maximal head motion. We feel this is a serious confound to this approach and recommend that interpretation of TCA that does not address motion and physiological noise be treated with caution. New techniques to localise epileptogenic activity with fMRI alone require validation with an appropriate independent measure. In the investigation of interictal epileptiform activity, this is best done with simultaneous EEG recording.

Cluster Analysis↗

Studying spontaneous EEG activity with fMRI.

The multifaceted technological challenge of acquiring simultaneous EEG-correlated fMRI data has now been met and the potential exists for mapping electrophysiological activity with unprecedented spatio-temporal resolution. Work has already begun on studying a host of spontaneous EEG phenomena ranging from alpha rhythm and sleep patterns to epileptiform discharges and seizures, with far reaching clinical implications. However, the transformation of EEG data into linear models suitable for voxel-based statistical hypothesis testing is central to the endeavour. This in turn is predicated upon a number of assumptions regarding the manner in which the generators of EEG phenomena may engender changes in the blood oxygen level dependent (BOLD) signal. Furthermore, important limitations are posed by a set of considerations quite unique to 'paradigmless fMRI'. Here, these issues are assembled and explored to provide an overview of progress made and unresolved questions, with an emphasis on applications in epilepsy.

Action Potentials↗

Functional MRI activation of individual interictal epileptiform spikes.

We used spike-triggered functional MRI in a patient with localization-related epilepsy to determine whether individual (as opposed to averaged) focal interictal epileptiform discharges (spikes) were associated with hemodynamic changes detectable with blood oxygen level-dependent functional MRI (fMRI). It was found that 15 of 43 spikes (34.9%) were associated with significant focal fMRI activation. Single event-related fMRI of interictal spikes is feasible in selected patients, giving complementary information to that provided by averaged fMRI data.

Brain Mapping↗

Landmark-based morphometrics of the normal adult brain using MRI.

We describe the application of statistical shape analysis to homologous landmarks on the cortical surface of the adult human brain. Statistical shape analysis has a sound theoretical basis. Landmarks are identified on the surface of a 3-D reconstruction of the segmented cortical surface from magnetic resonance image (MRI) data. Using publicly available software (morphologika) the location and size dependence of the landmarks are removed and the differences in landmark distribution across subjects are analysed using principal component analysis. These differences, representing shape differences between subjects, can be visually assessed using wireframe models and transformation grids. The MRI data of 58 adult brains (27 female and 15 left handed) were examined. Shape differences in the whole brain are described which concern the relative orientation of frontal lobe sulci. Analysis of all 116 hemispheres revealed a statistically significant difference (P < 0.001) between left and right hemispheres. This finding was significant for right- but not left-handed subjects alone. No other significant age, gender, handedness, or brain-size correlations with shape differences were found.

Adolescent↗

Event-related fMRI with simultaneous and continuous EEG: description of the method and initial case report.

We report on the initial imaging findings with a new technique for the simultaneous and continuous acquisition of functional MRI data and EEG recording. Thirty-seven stereotyped interictal epileptiform discharges (spikes) were identified on EEG recorded continuously during the fMRI acquisition on a patient with epilepsy. Localization of the BOLD activation associated with the EEG events was consistent with previous findings and EEG source modeling. The time course of activation was comparable with the physiological hemodynamic response function (HRF). The new methodology could lead to novel and important applications in many areas of neuroscience.

Cerebrovascular Circulation↗

Comparison of spike-triggered functional MRI BOLD activation and EEG dipole model localization.

We studied six patients with localization-related epilepsy, frequent interictal epileptiform discharges, and positive spike-triggered blood oxygen level-dependent functional MRI (BOLD-fMRI) findings. EEG source analysis solutions based on 64-channel EEG recorded in a separate session outside the scanner were obtained using dipole models and compared to the BOLD localization. The BOLD and structural images were coregistered, allowing the measurement of distances between the generator models and BOLD activation(s) and structural lesion when present. In all cases dipole models could be found that explained a sufficient amount of the data and that were anatomically concordant with the BOLD localization. In the five cases with structural abnormality visible on T1 scans, the BOLD activation overlapped or was in close proximity to the abnormality. The overall mean distance between the main moving dipole and the center of the nearest BOLD activation was 3.5 and 2.2 cm for the negative and positive peaks, respectively, including one case of a deep BOLD activation, in which the distance was 5 cm. In conclusion, the degree of agreement between the BOLD and EEG source localization indicates that the combination of these two noninvasive techniques offers the possibility of advancing the study of the generators of epileptiform electrical activity.

Adult↗

A study of the relationship between participation in common leisure activities and seizure occurrence.

OBJECTIVE: To investigate whether participation in a structured programme of fairly intensive leisure activities increased seizure occurrence. MATERIAL AND METHODS: 212 adults with medically-intractable epilepsy were closely monitored for seizure occurrence during an "activities day", i.e. a day consisting of various structured sessions of leisure pursuits (video game play, reading, word puzzles, television, physical exercise), and during other days of relative rest, whilst undergoing prolonged video EEG monitoring. RESULTS: The relative risk of seizures did not differ significantly during activities days [0.71 (95% CL: 0.38 to 1.33)] compared with days of relative rest. CONCLUSIONS: These findings fail to provide empirical support for the hypothesis that cognitive exertion has an adverse effect on seizure control.

Activities of Daily Living↗

Extrahippocampal temporal lobe atrophy in temporal lobe epilepsy and mesial temporal sclerosis.

Visual inspection and volumetric analysis of MRIs allow mesial temporal sclerosis (MTS) to be reliably identified in patients with temporal lobe epilepsy. The presence of unilateral MTS ipsilateral to the side of habitual seizure onset is an indicator for the prognosis of good outcome after temporal lobe resection. There is evidence to suggest that widespread temporal lobe pathology, leading to atrophy, may be associated with MTS and such abnormal tissue may play an important role in epileptogenesis. We have analysed quantitatively the volumes of the mesial and lateral temporal lobe substructures in MRIs from 62 patients with intractable mesial temporal lobe epilepsy and in 20 normal controls. We found significant atrophy in these structures in patients, ranging from 8.3 to 18.4% compared with controls. The degree of atrophy in the extrahippocampal structures correlated with the degree of hippocampal atrophy, suggesting that a common process may be responsible. There was no correlation between the degree of atrophy in the extrahippocampal structures and the duration of epilepsy, a history of febrile convulsions or of generalized seizures. These findings suggest that there may be widespread pathological abnormalities in the temporal lobe associated with MTS. The importance of extrahippocampal atrophy to surgical outcome and whether it occurs in temporal lobe epilepsy not associated with MTS remain to be investigated.

Adult↗

Spatio-temporal imaging of focal interictal epileptiform activity using EEG-triggered functional MRI.

EEG-triggered, blood oxygen level-dependent functional MRI (BOLD-fMRI) was used in 24 patients with localization-related epilepsy and frequent interictal epileptiform discharges (spikes) to identify those brain areas involved in generating the spikes, and to study the evolution of the BOLD signal change over time. The location of the fMRI activation was compared with the scalp EEG spike focus and the structural MR abnormality. Twelve patients (50%) had an fMRI activation concordant with the EEG focus and structural brain abnormalities where present (n = 7). In 2 other patients, the fMRI activation was non-concordant with electroclinical findings. The remaining 10 patients (41.7%) showed no significant fMRI activation. These patients had significantly lower mean spike amplitudes compared to those with positive fMRI results (p = 0.03). The time course of the BOLD response was studied in 3 patients and this revealed a maximum signal change 1.5 to 7.5 sec after the spike. In conclusion, EEG-triggered fMRI can directly identify the generators of interictal epileptiform activity, with high spatial resolution, in selected patients with frequent spikes. The superior spatial resolution obtainable through EEG-triggered fMRI may provide an additional non-invasive tool in the presurgical evaluation of patients with intractable focal seizures.

Action Potentials↗

EEG recording during fMRI experiments: image quality.

Electroencephalographic (EEG) monitoring during functional magnetic resonance imaging (fMRI) experiments is increasingly applied for studying physiological and pathological brain function. However, the quality of the fMRI data can be significantly compromised by the EEG recording due to the magnetic susceptibility of the EEG electrode assemblies and electromagnetic noise emitted by the EEG recording equipment. We therefore investigated the effect of individual components of the EEG recording equipment on the quality of echo planar images. The artifact associated with each component was measured and compared to the minimum scalp-cortex distance measured in normal controls. The image noise originating from the EEG recording equipment was identified as coherent noise and could be eliminated by appropriate shielding of the EEG equipment. It was concluded that concurrent EEG and fMRI could be performed without compromising the image quality significantly if suitable equipment is used. The methods described and the results of this study should be useful to other researchers as a framework for testing of their own equipment and for the selection of appropriate equipment for EEG recording inside a MR scanner.

Adolescent↗

Recovery of visual field constriction following discontinuation of vigabatrin.

Epilepsy patients treated with vigabatrin may develop symptomatic or asymptomatic concentric visual field constriction due to GABA-associated retinal dysfunction. The prevalence and course of this side effect are not established yet; in previously reported adult patients the visual disturbances seem to be irreversible. We present two patients with a significant improvement of visual field constriction and retinal function after the discontinuation of vigabatrin. These findings suggest that vigabatrin-associated retinal changes are at least partly reversible in some patients, and that these patients may benefit significantly from a withdrawal of vigabatrin. Larger scale clinical studies are needed to identify predictive factors both for the occurrence and reversibility of vigabatrin-associated visual field defects.

4-Aminobutyrate Transaminase↗

Remote memory in epilepsy.

PURPOSE: There is now a considerable amount of research relating to memory functioning in epilepsy. The majority of studies have focused on the retention of new information, and few reports have measured memory for past events. This study aims to redress this and measure the efficiency of remote memory in epilepsy. METHODS: A remote memory questionnaire was prepared and administered to three groups of patients with epilepsy and a control group without epilepsy. The questionnaire assessed knowledge of public events that occurred between 1980 and 1991, inclusive. The epilepsy groups comprised 33 patients with temporal lobe epilepsy (TLE), 33 with extratemporal epilepsy (ExTE), and 10 with primary generalized epilepsy (PGE). Thirty control subjects were tested. RESULTS: Patients with TLE performed significantly less well on the questionnaire than all other groups (p = 0.001), but no effect of laterality was recorded; patients with extratemporal or primary generalised epilepsy did not differ from controls. Performance on the questionnaire was not determined by verbal IQ, educational achievement, social class, or drug treatment, but was related to the number of generalised convulsions that had occurred since 1980. The strongest neuropsychological predictors of performance on this questionnaire were measures of verbal memory. CONCLUSIONS: The study demonstrated weak memory for past events in patients with TLE, thereby providing evidence of a broader memory disturbance in this group than has been previously highlighted. A test of remote memory, such as the one designed for this study, is easy to administer and provides clinically important information not available from conventional neuropsychological tests.

Achievement↗

Cardiac asystole in partial seizures.

Literature review shows many anecdotal case reports of cardiac asystole in ictal recordings of partial seizures. We have reviewed our data from the last five years, of patients who are being assessed for epilepsy surgery and found 2 out of more than 1,500 complex partial seizures, recorded in 589 consecutive patients, showing a significant period of asystole (13 and 15 seconds). Our previous studies of cardiac and respiratory parameters during partial seizures showed that a central apnoea occurred in 39%. It is probable that sudden death during seizures is due to the interaction of both cardiac and respiratory irregularities. Although rare (occurrence < 0.15%), the possibility of cardiac asystole occurring in an epilepsy monitoring unit highlights the need for resuscitation equipment to be readily available and for trained nursing staff. Furthermore, it is important to recognize that the semiology of seizures may be affected by the consequences of secondary cardiac asystole.

Adult↗

Disproportion in the distribution of gray and white matter: neuropsychological correlates.

OBJECTIVE: To examine the relationship between measures of disproportion in the regional distribution of gray and white matter and preoperative neuropsychological function in temporal lobe epilepsy patients with proved hippocampal sclerosis (HS). BACKGROUND: Subtle cerebral structural disruption, not evident on routine inspection of high-resolution MRI, is associated with poor surgical outcome in patients with histologically proved HS. Preoperative global memory dysfunction is also associated with poor postoperative seizure control. The authors hypothesize that patients with HS and abnormal regional distributions of gray and white matter would show more diffuse neuropsychological deficits preoperatively than patients with isolated HS alone. METHODS: A total of 28 adults with lateralized temporal lobe epilepsy and hippocampal volume loss measured on MRI were assessed preoperatively on neuropsychological tests of general intellect and the learning and recall of both verbal and nonverbal material. Quantitative MRI analysis of the regional distribution of gray and white matter was performed. Chi-square analyses were used to examine the relation between the presence or absence of cerebral abnormalities and preoperative performance on the neuropsychological tests. RESULTS: A total of 15 of 28 patients had extrahippocampal abnormalities on quantitative MRI analysis. Thirteen patients had global memory impairment. Bilateral memory deficits were significantly associated with both the presence of cerebral abnormalities (p < 0.02) and poor postoperative seizure control (p < 0.05). CONCLUSIONS: Disproportion in the regional distribution of gray and white matter in patients with HS may form the structural basis of global memory disturbance in a distinct group of patients with temporal lobe epilepsy.

Adult↗

Evidence for nodular epileptogenicity and gender differences in periventricular nodular heterotopia.

OBJECTIVE: To determine whether clinical differences between the sexes seen in periventricular nodular heterotopia (PNH) have structural correlates on imaging. BACKGROUND: PNH is the most common dysgenesis associated with hippocampal sclerosis (HS). Women with PNH have normal intellect; men may have mental retardation and other changes. Familial PNH, seen in women, is linked to Xq28-a region also abnormal in a sporadic male infant with PNH and retardation-suggesting sexual differences in gene expression. Epilepsy associated with PNH may be refractory to drugs, and surgery for associated HS does not stop seizures, suggesting intrinsic epileptogenicity of PNH. METHODS: Quantitative MRI analysis was performed using established techniques for detecting subtle structural changes in 13 female patients (11 sporadic and two familial) and four male patients (sporadic). RESULTS: There is structural heterogeneity in PNH, even in patients with bilateral PNH. On MRI, men have more cerebral abnormalities beyond PNH than control subjects or female patients (p < 0.005). CONCLUSIONS: The findings support the concept of intrinsic epileptogenicity of PNH. There may be additional structural abnormalities relevant to seizure generation, especially in men. Structural heterogeneity, and widespread abnormalities, may need consideration when patients are referred for surgical treatment or when additional studies of patients with PNH are conducted.

Adolescent↗

Reproducible localization of interictal epileptiform discharges using EEG-triggered fMRI.

We report preliminary experiences using fMRI triggered by EEG to localize the site of interictal epileptiform activity. EEG was recorded in the scanner and monitored on-line; the recording quality was good enough to allow the clear identification of spikes in the EEG. Snap-shot EPI was performed 2-4 s after an epileptiform discharge ('spike') or after at least 10 s of background activity ('rest') was observed. A pixel-by-pixel t-test was performed between the 'rest' and the 'spike' images to determine areas of significant activation. Significant activation was obtained in a patient with epilepsy. To assess the reliability and reproducibility of the technique, the patient was scanned on four separate occasions with similar areas being activated in all the studies, confirming the validity of the result.

Brain↗