Biomedical subjects

John S Duncan

Publications and source records attributed to John S Duncan.

At least 19 recordsLinked to original sources

PubMed2007

Statistical neuroanatomy of the human inferior frontal gyrus and probabilistic atlas in a standard stereotaxic space.

We manually defined the inferior frontal gyrus (IFG) on high-resolution MRIs in native space in 30 healthy subjects (15 female, median age 31 years; 15 male, median age 30 years), resulting in 30 individual atlases. Using standard software (SPM99), these were spatially transformed to a widely used stereotaxic space (MNI/ICBM 152) to create probabilistic maps. In native space, the total IFG volume was on average 5%, and the gray matter (GM) portion 12% larger in women (not significant). Expressed as a percentage of ipsilateral frontal lobe volume (i.e., correcting for brain size), the IFG was an average of 20%, and the GM portion of the IFG 27%, larger in women (P < 0.005). Correcting for total lobar volume yielded the same result. No asymmetry was found in IFG volumes. There were significant positional differences between the right and left IFGs, with the right IFG being further lateral in both native and stereotaxic space. Variability was similar on the left and right, but more pronounced anteriorly and superiorly. We show differences in IFG volume, composition, and position between sexes and between hemispheres. Applications include probabilistic determination of location in group studies, automatic labeling of new scans, and detection of anatomical abnormalities in patients.

Adult↗

PubMed2007

Temporal lobe interictal epileptic discharges affect cerebral activity in "default mode" brain regions.

A cerebral network comprising precuneus, medial frontal, and temporoparietal cortices is less active both during goal-directed behavior and states of reduced consciousness than during conscious rest. We tested the hypothesis that the interictal epileptic discharges affect activity in these brain regions in patients with temporal lobe epilepsy who have complex partial seizures. At the group level, using electroencephalography-correlated functional magnetic resonance imaging in 19 consecutive patients with focal epilepsy, we found common decreases of resting state activity in 9 patients with temporal lobe epilepsy (TLE) but not in 10 patients with extra-TLE. We infer that the functional consequences of TLE interictal epileptic discharges are different from those in extra-TLE and affect ongoing brain function. Activity increases were detected in the ipsilateral hippocampus in patients with TLE, and in subthalamic, bilateral superior temporal and medial frontal brain regions in patients with extra-TLE, possibly indicating effects of different interictal epileptic discharge propagation.

Auditory Cortex↗

PubMed2006

High-resolution diffusion tensor imaging of the hippocampus in temporal lobe epilepsy.

PURPOSE: To assess the quantitative diffusion characteristics of the hippocampus with high-resolution diffusion tensor imaging (DTI) in temporal lobe epilepsy (TLE). METHODS: Thirteen controls and seven unilateral TLE patients (six with hippocampal sclerosis, one with normal magnetic resonance imaging (MRI)) were scanned with DTI using a zonally magnified oblique multislice echo planar imaging (ZOOM-EPI) acquisition. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in the hippocampi. RESULTS: The mean hippocampal MD ipsilateral to the seizure focus was higher than the contralateral MD in patients (p<0.05) and the mean MD in controls (p<0.001). Hippocampal FA ipsilateral to the seizure focus was lower than the mean FA in controls (p<0.05). MD asymmetry indexes were significantly different between the patient and control groups (p<0.01). All six individual HS patients had ipsilateral hippocampal MD >or=2 standard deviations (S.D.) above the control mean. The patient with normal structural MRI had bilaterally low hippocampal FA and high MD. DISCUSSION: High-resolution DTI identifies lateralizing abnormalities of MD and FA in TLE patients. This quantitative data on hippocampal integrity may assist in evaluating TLE patients with normal MRI, and in longitudinal studies.

Adult↗

PubMed2006

Postictal diffusion weighted imaging.

PURPOSE: Our aim was to determine whether diffusion weighted imaging can detect abnormalities of diffusivity after single seizures, and investigate the localisation and time course of any changes. METHODS: Twenty-one patients with intractable focal epilepsy were imaged interictally and after 23 seizures. Voxel-based statistical parametric mapping was used to detect postictal changes in mean diffusivity (MD), compared to the changes noted in 20 controls scanned twice. The time course and magnitude of the changes were evaluated by measuring MD in the areas of change identified by the voxel-based analysis. RESULTS: Thirty-four focal changes in MD (24 decreases, 10 increases) were detected after 12 of 23 seizures in 11 patients, after a median interval of 53 min from the time of seizure onset. Five patients had areas of both increased and decreased diffusion after seizures. In four patients, postictal changes in diffusion corresponded with the presumed seizure focus. Repeated postictal scanning, after a further interval of a median of 46 min in eight patients, showed that postictal changes in MD, both increases and decreases, were returning towards interictal values. CONCLUSIONS: Diffusion weighted imaging identified focal changes in MD after 52% of single complex partial and secondarily generalised seizures. Changes in MD corresponded to the putative seizure focus in a minority of cases suggesting that the technique is not promising as a method for localising seizure foci, but may indicate the networks involved in seizures.

Adult↗

PubMed2006

Hemodynamic correlates of epileptiform discharges: an EEG-fMRI study of 63 patients with focal epilepsy.

Using continuous EEG-correlated fMRI, we investigated the Blood Oxygen Level Dependent (BOLD) signal correlates of interictal epileptic discharges (IEDs) in 63 consecutively recruited patients with focal epilepsy. Semi-automated spike detection and advanced modeling strategies are introduced to account for different EEG event types, and to minimize false activations from uncontrolled motion. We show that: (1) significant hemodynamic correlates were detectable in over 68% of patients in whom discharges were captured and were highly, but not entirely, concordant with site(s) of presumed seizure generation where known; (2) deactivations were less concordant and may non-specifically reflect the consequential or downstream effects of IEDs on brain activity; (3) a striking pattern of retrosplenial deactivation was observed in 7 cases mainly with focal discharges; (4) the basic hemodynamic response to IEDs is physiological; (5) incorporating information about different types of IEDs, their durations and saturation effects resulted in more powerful models for the detection of fMRI correlates; (6) focal activations were more likely when there was good electroclinical localization, frequent stereotyped spikes, less head motion and less background EEG abnormality, but were also seen in patients in whom the electroclinical focus localization was uncertain. These findings provide important new information on the optimal use and interpretation of EEG-fMRI in focal epilepsy and suggest a possible role for EEG-fMRI in providing new targets for invasive EEG monitoring.

Adult↗

PubMed2006

Hemispheric asymmetries in language-related pathways: a combined functional MRI and tractography study.

Functional lateralization is a feature of human brain function, most apparent in the typical left-hemisphere specialization for language. A number of anatomical and imaging studies have examined whether structural asymmetries underlie this functional lateralization. We combined functional MRI (fMRI) and diffusion-weighted imaging (DWI) with tractography to study 10 healthy right-handed subjects. Three language fMRI paradigms were used to define language-related regions in inferior frontal and superior temporal regions. A probabilistic tractography technique was then employed to delineate the connections of these functionally defined regions. We demonstrated consistent connections between Broca's and Wernicke's areas along the superior longitudinal fasciculus bilaterally but more extensive fronto-temporal connectivity on the left than the right. Both tract volumes and mean fractional anisotropy (FA) were significantly greater on the left than the right. We also demonstrated a correlation between measures of structure and function, with subjects with more lateralized fMRI activation having a more highly lateralized mean FA of their connections. These structural asymmetries are in keeping with the lateralization of language function and indicate the major structural connections underlying this function.

Adult↗

PubMed2006

EEG-fMRI of idiopathic and secondarily generalized epilepsies.

We used simultaneous EEG and functional MRI (EEG-fMRI) to study generalized spike wave activity (GSW) in idiopathic and secondary generalized epilepsy (SGE). Recent studies have demonstrated thalamic and cortical fMRI signal changes in association with GSW in idiopathic generalized epilepsy (IGE). We report on a large cohort of patients that included both IGE and SGE, and give a functional interpretation of our findings. Forty-six patients with GSW were studied with EEG-fMRI; 30 with IGE and 16 with SGE. GSW-related BOLD signal changes were seen in 25 of 36 individual patients who had GSW during EEG-fMRI. This was seen in thalamus (60%) and symmetrically in frontal cortex (92%), parietal cortex (76%), and posterior cingulate cortex/precuneus (80%). Thalamic BOLD changes were predominantly positive and cortical changes predominantly negative. Group analysis showed a negative BOLD response in the cortex in the IGE group and to a lesser extent a positive response in thalamus. Thalamic activation was consistent with its known role in GSW, and its detection in individual cases with EEG-fMRI may in part be related to the number and duration of GSW epochs recorded. The spatial distribution of the cortical fMRI response to GSW in both IGE and SGE involved areas of association cortex that are most active during conscious rest. Reduction of activity in these regions during GSW is consistent with the clinical manifestation of absence seizures.

Adolescent↗

PubMed2006

Adult epilepsy.

The epilepsies are one of the most common serious brain disorders, can occur at all ages, and have many possible presentations and causes. Although incidence in childhood has fallen over the past three decades in developed countries, this reduction is matched by an increase in elderly people. Monogenic Mendelian epilepsies are rare. A clinical syndrome often has multiple possible genetic causes, and conversely, different mutations in one gene can lead to various epileptic syndromes. Most common epilepsies, however, are probably complex traits with environmental effects acting on inherited susceptibility, mediated by common variation in particular genes. Diagnosis of epilepsy remains clinical, and neurophysiological investigations assist with diagnosis of the syndrome. Brain imaging is making great progress in identifying the structural and functional causes and consequences of the epilepsies. Current antiepileptic drugs suppress seizures without influencing the underlying tendency to generate seizures, and are effective in 60-70% of individuals. Pharmacogenetic studies hold the promise of being able to better individualise treatment for each patient, with maximum possibility of benefit and minimum risk of adverse effects. For people with refractory focal epilepsy, neurosurgical resection offers the possibility of a life-changing cure. Potential new treatments include precise prediction of seizures and focal therapy with drug delivery, neural stimulation, and biological grafts.

Adult↗

PubMed2006

EEG-fMRI mapping of asymmetrical delta activity in a patient with refractory epilepsy is concordant with the epileptogenic region determined by intracranial EEG.

We studied a patient with refractory focal epilepsy using continuous EEG-correlated fMRI. Seizures were characterized by head turning to the left and clonic jerking of the left arm, suggesting a right frontal epileptogenic region. Interictal EEG showed occasional runs of independent nonlateralized slow activity in the delta band with right frontocentral dominance and had no lateralizing value. Ictal scalp EEG had no lateralizing value. Ictal scalp EEG suggested right-sided central slow activity preceding some seizures. Structural 3-T MRI showed no abnormality. There was no clear epileptiform abnormality during simultaneous EEG-fMRI. We therefore modeled asymmetrical EEG delta activity at 1-3 Hz near frontocentral electrode positions. Significant blood oxygen level-dependent (BOLD) signal changes in the right superior frontal gyrus correlated with right frontal oscillations at 1-3 Hz but not at 4-7 Hz and with neither of the two frequency bands when derived from contralateral or posterior electrode positions, which served as controls. Motor fMRI activations with a finger-tapping paradigm were asymmetrical: they were more anterior for the left hand compared with the right and were near the aforementioned EEG-correlated signal changes. A right frontocentral perirolandic seizure onset was identified with a subdural grid recording, and electric stimulation of the adjacent contact produced motor responses in the left arm and after discharges. The fMRI localization of the left hand motor and the detected BOLD activation associated with modeled slow activity suggest a role for localization of the epileptogenic region with EEG-fMRI even in the absence of clear interictal discharges.

Brain Mapping↗

PubMed2006

Analysis of EEG-fMRI data in focal epilepsy based on automated spike classification and Signal Space Projection.

Simultaneous acquisition of EEG and fMRI data enables the investigation of the hemodynamic correlates of interictal epileptiform discharges (IEDs) during the resting state in patients with epilepsy. This paper addresses two issues: (1) the semi-automation of IED classification in statistical modelling for fMRI analysis and (2) the improvement of IED detection to increase experimental fMRI efficiency. For patients with multiple IED generators, sensitivity to IED-correlated BOLD signal changes can be improved when the fMRI analysis model distinguishes between IEDs of differing morphology and field. In an attempt to reduce the subjectivity of visual IED classification, we implemented a semi-automated system, based on the spatio-temporal clustering of EEG events. We illustrate the technique's usefulness using EEG-fMRI data from a subject with focal epilepsy in whom 202 IEDs were visually identified and then clustered semi-automatically into four clusters. Each cluster of IEDs was modelled separately for the purpose of fMRI analysis. This revealed IED-correlated BOLD activations in distinct regions corresponding to three different IED categories. In a second step, Signal Space Projection (SSP) was used to project the scalp EEG onto the dipoles corresponding to each IED cluster. This resulted in 123 previously unrecognised IEDs, the inclusion of which, in the General Linear Model (GLM), increased the experimental efficiency as reflected by significant BOLD activations. We have also shown that the detection of extra IEDs is robust in the face of fluctuations in the set of visually detected IEDs. We conclude that automated IED classification can result in more objective fMRI models of IEDs and significantly increased sensitivity.

Cerebral Cortex↗

PubMed2006

Memory fMRI in left hippocampal sclerosis: optimizing the approach to predicting postsurgical memory.

BACKGROUND: An optimal technique for clinical memory fMRI is not established. Previous studies suggest activity in right parahippocampal gyrus and right hippocampus shows the strongest difference between left hippocampal sclerosis (HS) patients and normal control subjects and that the difference in activity between left and right hippocampus predicts postoperative memory change. METHODS: The authors studied 30 patients with mesial temporal lobe epilepsy (mTLE) and left HS, 12 of whom subsequently underwent surgery, and 13 normal control subjects. The patients who had surgery underwent neuropsychometric evaluation pre- and postoperatively. All subjects underwent a verbal memory encoding event-related fMRI study. Activation maps were assessed visually. Subsequently, the brain regions involved in the memory task were revealed by group averaging; these regions were used to determine regions of interest (ROIs) for subsequent analysis. By use of stepwise discriminant function and stepwise multiple regression, the ROIs that optimally discriminated between patients and normal control subjects and that optimally predicted postoperative verbal memory outcome were determined. RESULTS: Visual inspection of individual patient activation statistic maps revealed noisy data that did not afford visual interpretation. Stepwise discriminant function revealed the difference between left and right hippocampal activity best discriminated between patients and normal control subjects. Stepwise multiple regression revealed left hippocampal activity was the strongest predictor of postoperative verbal memory outcome; greater left hippocampal activity predicted a greater postoperative decline in memory. CONCLUSIONS: Patients with left hippocampal sclerosis (HS) differ from normal control subjects in the distribution of memory-encoding activity between left and right hippocampus. Functional adequacy of left hippocampus best predicts postoperative memory outcome in left HS.

Epilepsy, Temporal Lobe↗

PubMed2006

Imaging the neocortex in epilepsy with double inversion recovery imaging.

The neocortices of 10 patients with partial seizures and acquired lesions, 14 patients with malformations of cortical development (MCD) and 33 patients with partial seizures and normal conventional MRI were quantitatively evaluated using whole brain double inversion recovery imaging (DIR) and Statistical Parametric Mapping (SPM). Compared to a group of 30 control subjects, DIR and objective voxel-by-voxel statistical comparison identified regions of significantly abnormal DIR signal intensity (DSI) in 9 out of 10 patients with acquired nonprogressive cerebral lesions and partial seizures. In all 9 patients, the areas of abnormal DSI concurred with abnormalities identified on visual inspection of conventional MRI. In all 14 patients with MCD, SPM detected regions of significantly abnormal DSI; all of which corresponded to abnormalities identified on visual inspection of conventional MRI. In addition, in both groups, there were areas that were normal on conventional imaging, which demonstrated abnormal DSI. Voxel-by-voxel statistical analysis identified significantly abnormal DSI in 15 of the 33 patients with cryptogenic focal epilepsy. In 10 of these, the areas of abnormal DSI concurred with epileptic EEG abnormality and clinical seizure semiology. Group analysis of MRI-negative patients with electroclinical seizure onset localising to the left temporal and left and right frontal regions revealed significantly abnormal DSI within the white matter of each respective lobe. DIR analysed using SPM was sensitive in patients with MCDs and acquired cerebral damage. Significant abnormalities in DSI in individual and grouped MRI-negative patients suggest that occult epileptogenic cerebral lesions are associated with subtle structural abnormalities. DIR is, therefore, a useful quantitative MRI technique for characterising epileptic foci and may contribute to presurgical evaluation.

Adult↗

PubMed2006

Magnetisation transfer ratio of choline is reduced following epileptic seizures.

The purpose of this study was to characterise the concentration and magnetisation transfer ratio (MTR) of brain metabolites following epileptic seizures. Magnetic resonance spectroscopy was performed in 10 patients with temporal or extra-temporal lobe epilepsy as soon as possible after a seizure, with a second interictal scan between 1 and 3 days after the postictal scan and 10 healthy controls were scanned twice. Voxels (26 +/- 2 mL) were placed in the frontal lobe in all patients and controls, on the side of seizure focus in the patient group. Spectra were obtained using a modified PRESS sequence (TE 30 ms, TR 3 s, with three hard pulses offset from the water frequency by 2,500 Hz for MT presaturation). Mean metabolite concentrations and median metabolite MTRs of N-acetylaspartate (NAA), creatine, choline (Cho), myo-inositol (Ins) and glutamate plus glutamine were compared between the first and second scans in each group. A significant decrease in the MTR of Cho was seen postictally in the patient group, but the metabolite concentrations showed no significant difference between interictal and postictal scans and in the control group there was no difference between the two scans. Inter-group comparison showed significantly reduced concentrations of NAA and Ins in the patients. Reduced MTR of Cho indicates a shift from a bound to a more mobile fraction. These changes might indicate membrane perturbation in areas of seizure spread.

Adult↗

PubMed2006

Paroxysmal motor disorders of sleep: the clinical spectrum and differentiation from epilepsy.

The diagnosis of paroxysmal events in sleep represents a significant challenge for the clinician, with the distinction of nocturnal epilepsy from nonepileptic sleep disorders often the primary concern. Diagnostic error or uncertainty is not uncommon in this situation, particularly with respect to nocturnal frontal lobe epilepsy (NFLE), which has a variable and often unusual presentation. Such errors can be minimized if the range of nonepileptic disorders with motor activity in sleep is fully appreciated. Here we review these disorders, before discussing the important clinical and electrographic features that allow their accurate differentiation from seizures. Particular emphasis is placed on the differentiation of nocturnal frontal lobe epilepsy from non-rapid eye movement (NREM) arousal disorders and other parasomnias. The value of recording episodes with video EEG polysomnography is discussed.

Adolescent↗

PubMed2005

Reading skills after left anterior temporal lobe resection: an fMRI study.

Maintaining language functions after left hemisphere lesions has been associated with compensatory right hemisphere activation. It remains unclear whether recruitment of right hemisphere regions necessarily provides an effective mechanism to compensate for language deficits. To investigate the compensatory mechanisms that mediate good reading skills in patients after left anterior temporal lobe resection for mesial temporal lobe epilepsy (mTLE), we tested for the effect of their reading ability on the regional fMRI (functional MRI) signal elicited by sentence reading. Sixteen control subjects and 16 patients participated in the study. In the activation condition, they silently read nine-word sentences, and in the baseline condition they viewed nine-word sentences after all the letters were transformed into false fonts. Reading ability in controls and patients significantly (P < 0.05, corrected) predicted activations in a left hemisphere middle temporal region that was part of the normal sentence reading system. In addition, reading ability in patients, but not controls, significantly predicted activation in the right inferior frontal sulcus, right hippocampus and right inferior temporal sulcus. Right inferior frontal activation was only observed in the patients. In contrast, right hippocampal and inferior temporal activation was observed in all controls and in patients whose reading ability was within the normal range, indicating the importance of these regions for efficient encoding during normal sentence reading. We conclude that proficient reading skills following left anterior temporal lobe resection for mTLE rely on two mechanisms: (i) integrating regions from the normal system (i.e. the left middle temporal, right hippocampus and anterior superior temporal sulcus); and (ii) recruiting right hemisphere regions (i.e. the right inferior frontal sulcus) that are not activated in control subjects.

Adult↗

PubMed2005

Magnetization transfer effect on human brain metabolites and macromolecules.

A pulse sequence was implemented to observe the magnetization transfer (MT) effect on metabolites, water, and macromolecules in human frontal lobes in vivo at 1.5 Tesla. Signals were compared following the application of three hard pulses of 0.745 muT amplitude, applied at frequency offsets of either 2500 Hz or 30 kHz, preceding a conventional point-resolved spectroscopy (PRESS)-localized acquisition with an echo time (TE) of 30 ms and repetition time (TR) of 3 s. This gave an MT effect on water in vivo of 46%, while direct saturation by the MT pulses at 2.5 kHz offset was confirmed to be under 4% for all metabolites. We observed significant MT saturation in vivo for N-acetylated compounds, choline (Cho), myo-inositol, and lactate (Lac); a trend of an effect on glutamate + glutamine (Glx); and the typically observed effect on creatine (Cr). No significant MT effect was seen on the macromolecule signal, which was observed using metabolite nulling.

Adolescent↗

PubMed2005

Postictal diffusion tensor imaging.

The objective of the study was to investigate postictal diffusion tensor imaging (DTI) in focal epilepsy. DTI and statistical parametric mapping (SPM) were used to examine objectively the diffusion properties of the brains of 18 patients with intractable focal epilepsy both postictally and interictally and to compare them with 27 normal controls scanned twice. Three sets of statistical tests were performed on each patient's fractional anisotropy and mean diffusivity data: interictal versus controls, postictal versus controls and a third "difference analysis" to test for significant changes in comparison with the differences noted between the two sets of control scans. Thirteen of the 18 patients (72%) had significant increases in mean diffusivity in the interictal scan. No decreases in mean diffusivity were detected. The difference analysis detected significant relative decreases in mean diffusivity postictally in nine patients (50%). These changes were focal in seven patients. In six of these, the site of the epileptic focus was known and co-localized with the diffusivity change in three. No significant changes in anisotropy were noted between the post- and interictal states. The postictal decrease in diffusivity probably reflects cellular swelling in the area of seizure onset and possibly areas of seizure spread. Postictal diffusivity changes appear complex and dynamic and timing after the seizure may be critical. Anisotropy measures appear less sensitive to these changes. Further systematic studies are needed and correlation with outcome after epilepsy surgery will determine the role of postictal diffusion measures in the presurgical evaluation of epilepsy patients.

Adult↗

PubMed2005

Epilepsy & depression: the effects of comorbidity on hippocampal volume--a pilot study.

Hippocampal sclerosis (HS) is one of the most common pathologies in medically intractable temporal lobe intractable epilepsy. Significant hippocampal volume loss has also been found in patients with chronic depression. Depression is common in chronic epilepsy populations, but the effects of this comorbidity on hippocampal volume are unknown. We examined the hippocampal volumes of 87 patients (n=31 right hippocampal sclerosis, RHS; n=56 left hippocampal sclerosis, LHS). Each subject completed the Hospital Anxiety and Depression Scale (HADS). In the group as a whole, 13 subjects (15%) recorded moderate or severe levels of depression. Depression was more common in the LHS group with 1 in 5 scoring in the moderate or severe range on the HADS (n=11). Depression scores were not significantly correlated with quantitative measures of hippocampal volume in the LHS group. However, higher degrees of hippocampal symmetry were associated with higher levels of depression in the RHS group. This suggests that the left hippocampus may be smaller in depressed patients with RHS, although our numbers were too small to confirm this statistically. Our results suggest that the depression may influence left hippocampal volume in patients with right hippocampal sclerosis. We conclude that the neuroradiological characteristics of patients with epilepsy and chronic depression deserve further examination.

Adult↗