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Biomedical subjects

R Mark Wellard

Publications and source records attributed to R Mark Wellard.

13 recordsLinked to original sources
PubMed2006

State, trait and biochemical influences on human anterior cingulate function.

The dorsal part of the human anterior cingulate cortex (dACC) is reliably activated in situations requiring cognitive control, especially during states of conflict. However, little is known about how individual differences in the neural characteristics of the dACC and major dimensions of behavior, affect this brain response. We recruited 28 healthy adults and employed a multi-modal neuroimaging approach combined with a task designed to specifically activate the human dACC and statistical path analysis to demonstrate clear roles for intelligence, personality and concentrations of neuronal N-acetylaspartate in determining dACC activation. These influences were comparable in magnitude to those associated with the experience of conflict. Our findings extend current understandings of the neural substrates of cognitive control by modeling the effect of neuronal viability, intelligence, and personality, on dACC activation. They also highlight the importance of considering enduring personal characteristics when mapping human brain-behavior relationships.

Adult↗
PubMed2006

Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations.

SCN1B, the gene encoding the sodium channel beta 1 subunit, was the first gene identified for generalized epilepsy with febrile seizures plus (GEFS+). Only three families have been published with SCN1B mutations. Here, we present four new families with SCN1B mutations and characterize the associated phenotypes. Analysis of SCN1B was performed on 402 individuals with various epilepsy syndromes. Four probands with missense mutations were identified. Detailed electroclinical phenotyping was performed on all available affected family members including quantitative MR imaging in those with temporal lobe epilepsy (TLE). Two new families with the original C121W SCN1B mutation were identified; novel mutations R85C and R85H were each found in one family. The following phenotypes occurred in the six families with SCN1B missense mutations: 22 febrile seizures, 20 febrile seizures plus, five TLE, three other GEFS+ phenotypes, two unclassified and ten unaffected individuals. All individuals with confirmed TLE had the C121W mutation; two underwent temporal lobectomy (one with hippocampal sclerosis and one without) and both are seizure free. We confirm the role of SCN1B in GEFS+ and show that the GEFS+ spectrum may include TLE alone. TLE with an SCN1B mutation is not a contraindication to epilepsy surgery.

Adolescent↗
PubMed2006

FMRI lateralization of expressive language in children with cerebral lesions.

PURPOSE: Lateralization of language function is crucial to the planning of surgery in children with frontal or temporal lobe lesions. We examined the utility of functional magnetic resonance imaging (fMRI) as a determinant of lateralization of expressive language in children with cerebral lesions. METHODS: fMRI language lateralization was attempted in 35 children (29 with epilepsy) aged 8-18 years with frontal or temporal lobe lesions (28 left hemisphere, five right hemisphere, two bilateral). Axial and coronal fMRI scans through the frontal and temporal lobes were acquired at 1.5 Tesla by using a block-design, covert word-generation paradigm. Activation maps were lateralized by blinded visual inspection and quantitative asymmetry indices (hemispheric and inferior frontal regions of interest, at p<0.001 uncorrected and p<0.05 Bonferroni corrected). RESULTS: Thirty children showed significant activation in the inferior frontal gyrus. Lateralization by visual inspection was left in 21, right in six, and bilateral in three, and concordant with hemispheric and inferior frontal quantitative lateralization in 93% of cases. Developmental tumors and dysplasias involving the inferior left frontal lobe had activation overlying or abutting the lesion in five of six cases. fMRI language lateralization was corroborated in six children by frontal cortex stimulation or intracarotid amytal testing and indirectly supported by aphasiology in a further six cases. In two children, fMRI language lateralization was bilateral, and corroborative methods of language lateralization were left. Neither lesion lateralization, patient handedness, nor developmental versus acquired nature of the lesion was associated with language lateralization. Involvement of the left inferior or middle frontal gyri increased the likelihood of atypical language lateralization. CONCLUSIONS: fMRI lateralizes language in children with cerebral lesions, although caution is needed in interpretation of individual results.

Adolescent↗
PubMed2005

Seizure-associated abnormalities in epilepsy: evidence from MR imaging.

Acute seizure-associated changes have been described in the animal and human literature. Controversy exists over whether seizures cause permanent damage to the brain, and whether a (prolonged) seizure can induce changes that lead to an epileptic lesion, resulting in habitual seizures and epilepsy. Current magnetic resonance imaging (MRI) offers a variety of imaging tools and is capable of detecting acute seizure-associated changes. In contrast to the histologic examination, serial MRI studies are possible and allow longitudinal observation of the fate of these changes. This report reviews the literature on acute seizure-associated effects emphasizing the MRI evidence.

Adult↗
PubMed2005

Physiologic variability of single-voxel proton MR spectroscopic measurements at 3T.

BACKGROUND AND PURPOSE: Physiologic and scanner variability of proton MR spectroscopy (MRS) measurements can limit the detection of subtle metabolite fluctuations. We assessed the variability of such measurements at 3T and compared two methods to obtain absolute concentrations. METHODS: Variability over 14 days was assessed with short-echo, single-voxel proton MRS in 14 control subjects and in a phantom containing 50 mmol/L N-acetylaspartate (NAA). Spectra were analyzed by using LCModel, scaling factors determined with both the calibration phantom (CP), and water peak intensity (WP) methods. Relative (reflecting the systematic drift) and absolute variability (reflecting the magnitude of scanner variability) was determined. RESULTS: For the phantom, initial (49 +/- 1.7 mmol/L) and second measurements (50 +/- 1.6 mmol/L) showed similar results, with small variability (relative, -0.6 +/- 1.5 mmol/L; absolute, 1.1 +/- 1.1 mmol/L). Control subjects had no systematic difference between the two scans for any measurement. Absolute variabilities in the temporal lobe for total NAA (NAA+NAAG) were 13% (CP) and 11% (WP). The largest variability (29%) was found for glutamate-glutamine (29%) with the CP method, and for myo-inositol with the WP method (28%). Absolute variability was smaller for the frontal lobe measurements (total NAA 7% and overall 6-18% for CP; total NAA 6% and overall 5-19% for WP). No significant difference was observed between the two methods. CONCLUSION: Physiologic variability is the major source of measurement variability and accounts for 12% of the variability in temporal lobe total NAA. Therefore, total NAA variations must clearly exceed this before they can reliably be attributed to an effect of disease.

Adult↗
PubMed2004

MR imaging and spectroscopic study of epileptogenic hypothalamic hamartomas: analysis of 72 cases.

BACKGROUND AND PURPOSE: Reports of MR imaging in hypothalamic hamartomas associated with epilepsy are few, and the number of patients studied is small. We aimed to detail the relationship of hypothalamic hamartomas to surrounding structures, to determine the frequency and nature of associated abnormalities, and to gain insight into mechanisms of epileptogenesis. METHODS: We systematically examined MR imaging studies of 72 patients with hypothalamic hamartoma and refractory epilepsy (patient age, 22 months to 31 years). A dedicated imaging protocol was used in 38 cases. Proton MR spectroscopy of the hypothalamic hamartoma was performed for 19 patients and compared with the metabolite profile of the thalamus in 10 normal children and the frontal lobe in 10 normal adults. RESULTS: Compared with normal gray matter, hypothalamic hamartomas were hyperintense on T2-weighted images (93%), hypointense on T1-weighted images (74%), and had reduced N-acetylaspartate and increased myoinositol content shown by MR spectroscopy. Hypothalamic hamartomas always involved the mammillary region of the hypothalamus, with attachment to one or both mammillary bodies. Intrahypothalamic extension (noted in 97%) tended to displace the postcommissural fornix and hypothalamic gray matter anterolaterally, such that the hypothalamic hamartomas nestled between the fornix, the mammillary body, and the mammillothalamic tract. Larger hamartoma size was associated with central precocious puberty. Associated findings of questionable epileptic significance included anterior temporal white matter signal intensity abnormalities (16%) and arachnoid cysts (6%). Malformations of cortical development were observed in only two patients, and hippocampal sclerosis was not observed. CONCLUSIONS: Hypothalamic hamartomas can be readily distinguished from normal hypothalamic gray and adjacent myelinated fiber tracts, best appreciated on thin T2-weighted images. MR imaging and spectroscopy suggest reduced neuronal density and relative gliosis compared with normal gray matter. Associated epileptogenic lesions are rare, supporting the view that the hypothalamic hamartoma alone is responsible for the typical clinical features of the syndrome. The intimate relationship to the mammillary body, fornix, and mammillothalamic tract suggests a role for these structures in epileptogenesis associated with hypothalamic hamartomas.

Adolescent↗
PubMed2003

Benign epilepsy with centro-temporal spikes: spike triggered fMRI shows somato-sensory cortex activity.

OBJECTIVE: We performed spike triggered functional MRI (fMRI) in a 12 year old girl with Benign Epilepsy with Centro-temporal Spikes (BECTS) and left-sided spikes. Our aim was to demonstrate the cerebral origin of her interictal spikes. METHODS: EEG was recorded within the 3 Tesla MRI. Whole brain fMRI images were acquired, beginning 2-3 seconds after spikes. Baseline fMRI images were acquired when there were no spikes for 20 seconds. Image sets were compared with the Student's t-test. RESULTS: Ten spike and 20 baseline brain volumes were analysed. Focal activiation was seen in the inferior left sensorimotor cortex near the face area. The anterior cingulate was more active during baseline than spikes. CONCLUSIONS: Left sided epileptiform activity in this patient with BECTS is associated with fMRI activation in the left face region of the somatosensory cortex, which would be consistent with the facial sensorimotor involvement in BECT seizures. The presence of BOLD signal change in other regions raises the possibility that the scalp recorded field of this patient with BECTs may reflect electrical change in more than one brain region.

Adolescent↗
PubMed2003

Myoinositol abnormalities in temporal lobe epilepsy.

PURPOSE: This study used magnetic resonance spectroscopy (MRS) to examine metabolite abnormalities in the temporal and frontal lobe of patients with temporal lobe epilepsy (TLE) of differing severity. METHODS: We investigated myoinositol in TLE by using short-echo MRS in 34 TLE patients [26 late onset (LO-TLE), eight hippocampal sclerosis (HS-TLE)], and 16 controls. Single-voxel short-echo (35 ms) MR spectra of temporal and frontal lobes were acquired at 1.5 T and analyzed by using LCModel. RESULTS: The temporal lobe ipsilateral to seizure origin in HS-TLE, but not LO-TLE, had reduced N-acetylaspartate (NA) and elevated myoinositol (MI; HS-TLE NA, 7.8 +/- 1.9 mM, control NA, 9.2 +/- 1.3 mM; p < 0.05; HS-TLE MI, 6.1 +/- 1.6 mM, control mI 4.9 +/- 0.8 mM, p< 0.05). Frontal lobe MI was low in both patient groups (LO-TLE, 4.3 +/- 0.8 mM; p < 0.05; HS-TLE, 3.6 +/-.05 mM; p < 0.001; controls, 4.8 +/- 0.5 mM). Ipsilateral frontal lobes had lower MI (3.8 +/- 0.7 mM; p < 0.01) than contralateral frontal lobes (4.3 +/- 0.8 mM; p < 0.05). CONCLUSIONS: MI changes may distinguish between the seizure focus, where MI is increased, and areas of seizure spread where MI is decreased.

Adult↗
PubMed2003

MR imaging of epilepsy: state of the art at 1.5 T and potential of 3 T.

Shortly after being introduced in the nineteen eighties, magnetic resonance imaging (MRI) became a key tool for the investigation of patients with epilepsy, due to its ability to acquire high quality images. The strength of the magnetic field of a scanner is measured in tesla (T). This review addresses the clinical and research potential in epilepsy of MR imaging at 1.5 T and 3 T. A typical clinical scanning protocol at 1.5 T for a patient with refractory epilepsy may include T1- and T2-weighted imaging, fluid-attenuated inversion recovery (FLAIR) imaging, and a 3D volume acquisition sequence. A research protocol may add quantification of structural imaging, such as volumetric assessment and T2-relaxometry, together with functional measures, such as MR-spectroscopy, functional MRI and diffusion weighted sequences. MR-spectroscopy assesses the metabolites of the seizure focus and other brain areas. Functional MRI allows localisation of cognitive and sensori-motor function and the ability to assess the spatial relationship of these functions to the seizure focus. Whereas these techniques can be performed at 1.5 T, particularly MR-spectroscopy and functional MRI benefit from increased magnetic field-strength. Higher magnetic field-strength is associated with a higher signal-to-noise ratio (SNR). The increased SNR can allow shorter imaging times for a given resolution, higher resolution for a given imaging time, or combination of both. The use of higher magnetic field-strengths is therefore indicated for the (fast) imaging of ill subjects, for long protocols, including structural, metabolic and functional imaging, and for novel applications, such as continuous EEG recording and functional MRI for the detection of the seizure focus. Disadvantages of MR imaging in epilepsy at a high field-strength of 3 T and above are, apart from engineering and technical challenges, the greater energy deposition into tissue and increased susceptibility to artefacts. So far, magnets of 3 T and above have been used mainly for research applications, however the benefits of high field-strength for MR spectroscopy and functional MRI, and the usefulness of these techniques for the investigation of epilepsy patients are obvious incentives for the use of 3 T systems in routine clinical investigations.

Electroencephalography↗
PubMed2002

Implications of lipid biology for the pathogenesis of schizophrenia.

OBJECTIVE: Preclinical and clinical data suggest that lipid biology is integral to brain development and neurodegeneration. Both aspects are proposed as being important in the pathogenesis of schizophrenia. The purpose of this paper is to examine the implications of lipid biology, in particular the role of essential fatty acids (EFA), for schizophrenia. METHODS: Medline databases were searched from 1966 to 2001 followed by the cross-checking of references. RESULTS: Most studies investigating lipids in schizophrenia described reduced EFA, altered glycerophospholipids and an increased activity of a calcium-independent phospholipase A2 in blood cells and in post-mortem brain tissue. Additionally, in vivo brain phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS) demonstrated lower phosphomonoesters (implying reduced membrane precursors) in first- and multi-episode patients. In contrast, phosphodiesters were elevated mainly in first-episode patients (implying increased membrane breakdown products), whereas inconclusive results were found in chronic patients. EFA supplementation trials in chronic patient populations with residual symptoms have demonstrated conflicting results. More consistent results were observed in the early and symptomatic stages of illness, especially if EFA with a high proportion of eicosapentaenoic acid was used. CONCLUSION: Peripheral blood cell, brain necropsy and 31P-MRS analysis reveal a disturbed lipid biology, suggesting generalized membrane alterations in schizophrenia. 31P-MRS data suggest increased membrane turnover at illness onset and persisting membrane abnormalities in established schizophrenia. Cellular processes regulating membrane lipid metabolism are potential new targets for antipsychotic drugs and might explain the mechanism of action of treatments such as eicosapentaenoic acid.

Fatty Acids, Essential↗
PubMed2002

A sheep model for the study of focal epilepsy with concurrent intracranial EEG and functional MRI.

PURPOSE: We describe a sheep model of penicillin-induced seizure activity using electroencephalography (EEG) and functional MRI (fMRI). METHODS: Ten adult sheep were used. Spikes and seizures were generated by instillation of 8,000-10,000 IU of penicillin into the right prefrontal cortex via a specially designed port. Bilateral intracranial EEG was acquired by using carbon fiber electrodes. Animals had behavioral characterization of their seizures and were then anesthetized for fMRI studies. Functional MRI was performed at 1.5 and 3 Tesla by measuring blood oxygen level-dependent (BOLD) weighted signal intensity at different times during the evolution of seizures. RESULTS: Behavioral seizures were associated with electrographic seizures. Intracranial EEG obtained in the MR scanner was of high quality. Focal spiking and seizures were seen in all animals and developed 11.3 +/- 11.2 s and 17.3 +/- 12.1 min after penicillin administration, respectively. An average of 13 +/- 4.8 seizures were seen per animal, each lasting 27.3 +/- 12.3 s. Functional MR images with little parenchymal artefact were obtained. Regional BOLD signal-intensity changes were observed during seizures at the seizure focus and ipsilateral amygdala. CONCLUSIONS: We have developed an animal model of partial epilepsy in which seizures can be reliably elicited with concurrent fMRI and intracranial EEG. During unilateral electrographic seizures, focal BOLD signal changes occurred at the seizure focus and ipsilateral amygdala, suggesting the presence of a cortico-subcortical loop. This observation illustrates the potential of the model for understanding seizure generation, spread, and possibly the consequences of repeated seizures on the brain.

Animals↗
PubMed2002

Differential functional magnetic resonance imaging language activation in twins discordant for a left frontal tumor.

Eight-year-old twins, one with a left frontal tumor and aphasic seizures, the other neurologically normal, underwent serial assessment of expressive language with functional magnetic resonance imaging and neuropsychology. The affected twin showed a significant amount of right hemisphere activation coincident with behavioral deterioration in expressive language and late growth in the tumor. This pattern of language dysfunction and the left language dominance of her co-twin suggested that the affected twin was also left dominant for language, and the significance of her right activation is discussed. We postulate that the right hemisphere activation represents a stabilizing mechanism in the context of a developmental and progressive lesion in language cortex rather than language transfer per se.

Brain Neoplasms↗