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Biomedical subjects

Anthony B Waites

Publications and source records attributed to Anthony B Waites.

6 recordsLinked to original sources

How reliable are fMRI-EEG studies of epilepsy? A nonparametric approach to analysis validation and optimization.

Simultaneously acquired functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) data hold great promise for localizing the spatial source of epileptiform events detected in the EEG trace. Despite a number of studies applying this method, there has been no independent and systematic validation of the approach. The present study uses a nonparametric method to show that interictal discharges lead to a blood oxygen level dependent (BOLD) response that is significantly different to that obtained by examining random 'events'. We also use this approach to examine the optimization of analysis strategy for detecting these BOLD responses. Two patients with frequent epileptiform events and a healthy control were studied. The fMRI data for each patient were analyzed using a model derived from the timings of the epileptiform events detected on EEG during fMRI scanning. Twenty sets of random pseudoevents were used to generate a null distribution representing the level of chance correlation between the EEG events and fMRI data. The same pseudoevents were applied to control data. We demonstrate that it is possible to detect blood oxygen level-dependent (BOLD) changes related to interictal discharges with specific and independent knowledge about the reliability of this activation. Biologically generated events complicate the fMRI-EEG experiment. Our proposed validation examines whether identified events have an associated BOLD response beyond chance and allows optimization of analysis strategies. This is an important step beyond standard analysis. It informs clinical interpretation because it permits assessment of the reliability of the connection between interictal EEG events and the BOLD response to those events.

Analysis of Variance↗

Effect of prior cognitive state on resting state networks measured with functional connectivity.

To address the extent to which functional connectivity measures an absolute brain state, we observed the effect of prior performance of a language task on resting-state networks in regions associated with language. Six subjects were imaged during rest before and after a block-design language task. Connectivity maps were generated for each of four language regions (identified from analysis of the language activation portion of the study) in each subject for both rest periods. Conjunction analysis demonstrated distinct networks of voxels for each seed region, indicating separate functional subnetworks associated with the different regions. In a comparison of rest before and after the activation task widespread and significant changes were observed in all individuals, suggesting that the measured resting state network reflects a dynamic image of the current brain state. At the group level, an extended network was observed that was largely persistent over time. Even at the group level an increase in connectivity was observed between left and right middle frontal gyri, and between posterior cingulate cortex and medial frontal cortex in the rest after the language task. These results suggest that functional connectivity may be a powerful measure of cognitive state, sensitive to differences between controls and patients together with the particular cognitive processing occurring during the rest state.

Brain Mapping↗

A high-field functional MRI study of quadri-lingual subjects.

We assessed six multilingual subjects by functional MRI using a Noun Verb Generation task in four different languages. We hypothesised that the degree of proficiency in each language would be related to the extent of functional activity measured in a region of interest analysis. Proficiency in each language was quantified using two neuropsychological tests. All four languages activated overlapping brain areas, corresponding to the major language regions. The number of activated voxels correlated with proficiency, so that the activated volume increased for languages in which a subject had poorer proficiency. Activation did not appear to be dependent on the age at which the language was learnt.

Adult↗

Voxel-based relaxometry: a new approach for analysis of T2 relaxometry changes in epilepsy.

The measurement of the T2 relaxation time (T2 relaxometry) had been established as a reliable tool for the assessment of certain conditions such as temporal lobe epilepsy. The standard procedure for analysis of T2 data uses manually drawn regions of interest (ROIs). This approach is limited by its subjective nature and its restricted scope of investigation within selected regions of the brain. In this study, we introduce a voxel-based analysis approach termed voxel-based relaxometry (VBR). Tissue signal changes were assessed in 19 patients with hippocampal sclerosis (HS) and in 38 healthy controls using (i) conventional ROI-based analysis with several bilateral ROIs and also (ii) the VBR method in which the T2 maps are warped to a stereotactic space, smoothed and statistically compared. Conventional ROI analysis identified the expected T2 increase in the sclerotic hippocampus in all HS patients. Furthermore, 13 of the 19 patients displayed a T2 increase in at least one of the other ROIs. The VBR analysis showed a similar pattern of statistically significant areas of increased T2 within the sclerotic hippocampus. In addition, extrahippocampal areas of increased T2 were apparent including the anterior temporal lobe white matter and the parahippocampal gyrus. The results of the VBR analysis are in agreement with the conventional ROI analysis. The VBR analysis has the advantage of providing an even-handed assessment of T2 differences through the brain. We recommend VBR as an alternative means of relaxometry data analysis that provides an objective assessment of differences between subjects.

Adult↗

fMRI "deactivation" of the posterior cingulate during generalized spike and wave.

Using spike-triggered fMRI, we sought to document regional changes in blood oxygen level-dependent (BOLD) activity associated with spontaneous generalised spike and slow-wave discharges (S&W). Five adult patients were studied who had idiopathic generalised epilepsy (IGE) and frequent S&W. EEG was recorded inside a 3T MRI, allowing acquisition of single, whole-brain fMRI images following S&W, as well as baseline images. Between 4 and 25 spike and wave complexes were captured in individuals. Four of the five individuals showed significant S&W-related BOLD signal reductions ("deactivation") in the posterior cingulate (P<0.001 uncorrected). Significant changes were absent only in the individual with fewest spikes. Group analysis including all five subjects confirmed fMRI deactivation in the posterior cingulate. Some S&W-related BOLD signal increases were seen in the depths of the precentral sulci in individuals and on group analysis. No significant S&W-related changes in thalamic BOLD activity were observed. The posterior cingulate may have a role in the electroclinical phenomenon of S&W and "absence." Possibilities include a causative role, with reduced activity in the cingulate facilitating the onset of S&W, a secondary role, explaining the cognitive changes observed during prolonged S&W, or an epiphenomenon.

Adolescent↗

Correlation between language organization and diffusion tensor abnormalities in refractory partial epilepsy.

PURPOSE: Atypical language organization is more frequently found in patients with refractory partial epilepsy than in healthy controls; however, the reasons for this are not well known. Here we assess the relation between language laterality index (LI) and white-matter tract changes. METHODS: Nine patients with refractory partial epilepsy were assessed with a 3-T GE scanner. Functional magnetic resonance imaging (fMRI) of language and diffusion tensor imaging (DTI) were acquired. For the fMRI, a noun-verb generation task was performed, all images were motion corrected, and activated pixels in classic language areas were counted. The DTI images were acquired in six standard directions with an initial non-diffusion-weighted scan. The "average anisotropy" was determined in a region of interest in the frontal lobe, temporal lobe, and parietal lobe white matter. An asymmetry index (AI) was calculated for language and DTI. Atypical language lateralization was diagnosed if the lateralization index (LI)-language was smaller than 0.4. RESULTS: Two of the nine patients had atypical language localization (LI-language, -0.6, and 0.3); both had left temporal DTI asymmetry (LI-DTI, -0.3 and -0.2). The remaining seven patients had typical language localization, and no marked DTI abnormalities. Asymmetry in temporal lobe DTI correlated with LI-language (r= 0.8; p = 0.006). CONCLUSIONS: Atypical language lateralization in patients with partial epilepsy may be associated with white-matter tract abnormalities.

Adolescent↗