Biomedical subjects

Graeme D Jackson

Publications and source records attributed to Graeme D Jackson.

At least 19 recordsLinked to original sources

PubMed2006

Functional connectivity networks are disrupted in left temporal lobe epilepsy.

OBJECTIVE: Functional connectivity maps the distributed network of brain regions fluctuating synchronously during a continuous brain state. This study sought to investigate whether patients with left temporal lobe epilepsy (TLE) differ from controls in their resting-state functional connectivity between typical language regions. METHODS: We studied 17 patients with left TLE, together with eight healthy controls, using seeded functional connectivity. Seed regions were defined using the regions of maximal activation and deactivation during a language functional magnetic resonance imaging (fMRI) task in a separate cohort of 30 controls. RESULTS: Language fMRI produced the expected activation pattern, which was not different between patients and controls. However, functional connectivity between language areas during rest was markedly different; whereas controls showed connectivity between each of the seed areas and the majority of the language areas, patients showed connectivity only with a few areas, particularly the seed area itself. This difference was significant in the direct comparison of patients and control connectivity maps. INTERPRETATION: We suggest that this reduced connectivity in left temporal lobe epilepsy may reflect a disturbance of the language network during resting state in patients and may be related to subtle language difficulties in this patient population.

Adult↗

PubMed2006

Optimized clinical T2 relaxometry with a standard CPMG sequence.

PURPOSE: To optimize the accuracy and precision of T2 measurements using the standard Carr-Purcell-Meiboom-Gill (CPMG) sequence. T2 values obtained with this technique are normally sensitive to imperfect refocusing due to the formation of unwanted stimulated echoes. MATERIALS AND METHODS: Modifications are made to the refocusing slice selection width and the interleaving scheme. A widened refocusing slice improves the uniformity of the refocusing flip angle across the slice. A slow spin echo acquisition provided "gold standard" T2 values. Repeated T2 measurements in phantom and human studies are used to compare the accuracy and precision of the optimized and non-optimized CPMG implementations. RESULTS: The required slice thickness ratio between refocusing and excitation slice widths is found to be 3:1 for typical optimized radiofrequency pulses. T2 values obtained using this optimized implementation more closely correspond to "gold standard" values. Repeated T2 measurements indicate significantly improved correspondence between data and model. A reduction in the fitting error of approximately 70% is demonstrated for phantoms. CONCLUSION: We demonstrate that a relatively simple change to the CPMG relaxometry sequence parameters from the default setup yields significant improvements in the accuracy and precision of T2 measurements.

Adult↗

PubMed2006

Further steps toward direct magnetic resonance (MR) imaging detection of neural action currents: optimization of MR sensitivity to transient and weak currents in a conductor.

The characteristics of an MRI technique that could be used for direct detection of neuronal activity are investigated. It was shown that magnitude imaging using echo planar imaging can detect transient local currents. The sensitivity of this method was thoroughly investigated. A partial k-space EPI acquisition with homodyne reconstruction was found to increase the signal change. A unique sensitivity to the position of the current pulse within the imaging sequence was demonstrated with the greatest signal change occurring when the current pulse coincides with the acquisition of the center lines of k-space. The signal change was shown to be highly sensitive to the spatial position of the current conductor relative to the voxel. Furthermore, with the use of optimization of spatial and temporal placement of the current pulse, the level of signal change obtained at this lower limit of current detectability was considerably magnified. It was possible to detect a current of 1.7 microA applied for 20 ms with an imaging time of 1.8 min. The level of sensitivity observed in our study brings us closer to that theoretically required for the detection of action currents in nerves.

Action Potentials↗

PubMed2006

Thalamic atrophy in childhood absence epilepsy.

PURPOSE: Patients with childhood absence epilepsy (CAE) have normal clinical magnetic resonance imaging (MRI) studies. The presence of abnormalities in corticothalamic networks has been suggested to be the functional basis of absence seizure generation. We assessed whether structural grey and white matter volume changes of these areas occurred in patients with absence seizures by using optimized voxel-based morphometry (VBM). METHODS: We recruited 13 patients with a clinical and EEG diagnosis of CAE (mean age at examination, 17 +/- 8 years) and compared them with a consecutive series of 109 controls (mean age, 29 +/- 9 years). The 3 tesla MRI examination included a 3D T(1)-weighted sequence, which was analyzed with an optimized VBM protocol using the SPM2 package. The threshold was set at p < 0.05, corrected for multiple comparisons. RESULTS: Compared with controls, CAE patients showed areas of grey matter decrease in both thalami and in the subcallosal gyrus. White matter decrease was found in the extranuclear subcortical area and in the white matter of the basal forebrain. Grey and white matter increase was restricted to small clusters of cortical and subcortical areas. CONCLUSIONS: Evidence exists of subcortical grey and white matter volume reduction in CAE patients. Bilateral thalamic atrophy may be either a result of damage from seizures (as in hippocampal sclerosis) or a reflection of a primary underlying pathology as the cause of absence seizures.

Adolescent↗

PubMed2006

Is language lateralization in temporal lobe epilepsy patients related to the nature of the epileptogenic lesion?

PURPOSE: Early acquired lesions are considered to be a risk factor for atypical language lateralization in epilepsy, whereas developmental lesions are not. Hippocampal sclerosis (HS) can be understood as an early, acquired lesion, whereas developmental tumors (DT) are thought to originate in utero. We assessed whether language lateralization differs between these groups of temporal lobe epilepsy patients. METHODS: We used 3-Tesla functional MRI (fMRI) to assess 41 patients (16 DT, 25 HS) and 50 controls, performing a noun-verb-generation task. fMRI data were processed by using SPM2. A laterality index (LI) was calculated based on the number of activated voxels in left- and right-sided frontal lobe language areas. Atypical lateralization was considered if the index was < or = 0.2. RESULTS: Patients had a lower LI (0.42 +/- 0.5) than controls (0.6 +/- 0.3; p < or = 0.05), but the LI was not different between DT (0.44 +/- 0.5) and HS patients (0.43 +/- 0.4; p = 0.9). The frequency of atypical lateralization was increased in patients (27%) compared with controls (8%) but was similar in both patient groups (DT, 31%; HS, 24%). HS patients had an earlier onset and longer duration of epilepsy and a higher frequency of significant antecedent events (p < or = 0.05). CONCLUSIONS: Patients with TLE demonstrate a deviation toward atypical language lateralization. However, language lateralization was not different between patients with presumably acquired lesions compared with patients with developmental pathology. This suggests that the nature of the temporal lobe lesion does not influence overall language lateralization.

Adult↗

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↗

PubMed2006

Event-related fMRI of myoclonic jerks arising from dysplastic cortex.

BACKGROUND: Malformations of cortical development can cause epileptiform activity and myoclonic jerks, yet EEG correlates of jerks can be difficult to obtain. METHODS: We studied a woman who had frequent episodes of persistent right-foot jerking since childhood. Ictal and interictal EEG had shown no localizing epileptiform activity. Functional imaging experiments were performed with concurrent video monitoring to document the timing of foot jerks. These studies mapped brain regions controlling voluntary right- and left-foot movements, and spontaneous right-foot jerks. RESULTS: High-resolution structural MR imaging revealed a dysplastic gyrus extending anteriorly off the left central sulcus. Event-related analysis of spontaneous jerks revealed prominent activation of the left precentral gyrus (right-foot motor area), bilateral medial frontal regions (supplementary motor area), and the dysplastic gyrus. Hemodynamic response modeling to foot jerks revealed the hemodynamic response peaked earlier in the dysplastic cortex and SMA regions than in the foot area. DISCUSSION: Event-related fMRI in a patient with spontaneous and induced epileptic foot jerks revealed brain regions active during jerks. The results of this analysis allowed us to tailor subsequent intracerebral recordings. Analysis of the timing of the hemodynamic response showed certain brain regions with an earlier rise in BOLD signal, suggesting a possible initiating role, or different hemodynamic response functions. Hemodynamic response timing should be considered carefully when interpreting event-related studies of epileptiform activity.

Adult↗

PubMed2005

Functional MRI of the pre-ictal state.

The mechanisms underlying the transition from interictal to ictal states are poorly understood. Non-linear mathematical analysis of EEG frequency components has confirmed the presence of a pre-ictal state in focal epilepsy. We report on functional MRI (fMRI) analysis of the pre-ictal state in three patients with intractable focal epilepsy. Each subject had a typical partial seizure in the scanner while continuous blood oxygen level dependent (BOLD) fMRI images were acquired. The pre-ictal BOLD changes were first analysed by statistically comparing BOLD signals of two one-minute blocks. Further examination of the full time course was then performed. Each patient showed highly significant, focal BOLD signal changes. In Patient 1, a striking pre-ictal BOLD signal increase was seen over the region of the seizure focus identified on complementary epilepsy investigations. No significant BOLD signal decreases were observed. Patient 2 showed widespread pre-ictal BOLD increase contralateral to the presumed seizure focus, as well as a focal BOLD decrease near the presumed seizure focus. In Patient 3, pre-ictal BOLD increase was co-localized with the site of hyperperfusion seen on ictal single photon emission computed tomography (SPECT). However, this was contralateral to the seizure focus localization based on seizure symptomatology. No significant BOLD decreases were seen. The time course data in each patient studied showed change of the BOLD signal several minutes before the onset of the seizure. Highly significant BOLD fMRI signal changes occur before the onset of seizures, supporting the presence of a pre-ictal state. These changes can be localized to the site of the presumed seizure focus, as well as to other brain regions, suggesting that the pre-ictal BOLD signal changes and their underlying mechanisms are complex.

Adolescent↗

PubMed2005

Cortical/subcortical BOLD changes associated with epileptic discharges: an EEG-fMRI study at 3 T.

BACKGROUND: Malformations of cortical development have characteristic interictal discharges, yet the mechanisms of generation of these discharges are not known in humans. Interictal discharges in malformations of cortical development were studied with EEG-fMRI. METHODS: Six subjects with malformations of cortical development and seizures were studied using spike-triggered fMRI at 3 T. The blood oxygen level-dependent (BOLD) signal changes associated with interictal discharges were measured. RESULTS: All subjects showed spike-related BOLD signal changes. In four subjects, the signal increases were seen in the lesion, and in four subjects, decreases were seen surrounding the lesion. Five subjects had BOLD signal changes at distant cortical sites and three had subcortical changes (basal ganglia, reticular formation, or thalamic). CONCLUSION: BOLD signal changes may be directly correlated with overall synaptic activity. Changes were found in and around the lesion of malformations of cortical development and in distant cortical and subcortical structures. The results suggest that EEG-fMRI studies might help elucidate the mechanisms of epileptic discharges in humans.

Action Potentials↗

PubMed2005

Cerebral structural changes in severe obstructive sleep apnea.

Obstructive sleep apnea is associated with abnormalities in neuropsychologic function, and defects in respiratory control may contribute to pathogenesis. Abnormalities may be reflected in structural brain changes. Twenty-seven male untreated patients with severe sleep apnea without comorbidities, and 24 age-matched control subjects, had T1-weighted brain imaging in a high-resolution magnetic resonance scanner. Twenty-three patients with sleep apnea had repeat imaging after 6 months of continuous positive airways pressure treatment. No areas of gray matter volume change were found in patients using an optimized voxel-based morphometry technique, at p < 0.05 adjusted for multiple comparisons (despite the method being sensitive to changes in gray matter fraction of 0.17 or less in all voxels). Furthermore, no differences were seen in bilateral hippocampal, temporal lobe, or whole brain volumes, assessed by manual tracing of anatomical borders. No longitudinal changes were seen in gray matter density or regional volumes after treatment, but whole brain volume decreased slightly. We have found no gray matter volume deficits nor focal structural changes in severe obstructive sleep apnea. Whole brain volume decreases without focal changes after 6 months of continuous positive airways pressure treatment.

Adult↗

PubMed2005

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↗

PubMed2005

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↗

PubMed2005

Brief breath holding may confound functional magnetic resonance imaging studies.

We demonstrate that breath holding of short durations may confound functional magnetic resonance imaging (fMRI) studies. Some subjects may hold their breath for a short time during task performance, especially if the task is challenging. Breath holding may therefore need to be considered specifically when interpreting fMRI experiments. We studied the temporal and spatial characteristics of cerebral T2*-weighted signal during short periods of breath holding by seven individuals in a 3-tesla MR scanner. We demonstrate that breath-holds as short as 3 s can result in regions of significant cerebral activation. More interestingly, we show that focal activation remains present when the data is analysed in a number of different ways, including analyses that correct for motion and model the task epoch as if it were 10 times longer than the actual breath-hold length. These findings have potential relevance for many researchers carrying out fMRI studies.

Adult↗

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↗

PubMed2005

Typical childhood absence seizures are associated with thalamic activation.

Functional MRI with simultaneously acquired EEG (fMRI/EEG) can identify areas of signal change associated with interictal discharges. We report the fMRI/EEG study of a child with newly-diagnosed IGE, performed prior to the start of antiepileptic medication. The 7-years-old girl had very frequent absences, associated with eyelid myoclonia. Her EEG showed frequent, typical 3/sec discharges. Functional MRI was performed with a 3T scanner using whole brain gradient echo-planar imaging, and the EEG was recorded with 18, non-metallic, scalp electrodes. Ten bursts of generalized discharges were captured during 30 minutes fMRI/EEG acquisition. The bursts lasted 3.4 (SD +/- 0.6) seconds. Event-related analysis was performed with SPM2 and iBrain software. Functional MRI showed prominent, bilateral thalamic activation, and less pronounced areas of cortical activation and deactivation. This study demonstrates thalamic activation in typical, untreated childhood absence epilepsy. The cortical signal change may be related to a thalamo-cortical circuit.

Brain Mapping↗

PubMed2004

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↗

PubMed2004

Stable ratio of ipsilateral to contralateral sensory motor cortex activity despite varying effort and peripheral nerve block.

BACKGROUND: Ipsilateral sensory motor cortex (SMC) activation can occur during hand movements following cerebral injury. We studied the effect of increasing task difficulty and temporary peripheral paralysis on patterns of motor system activation. METHODS: Six healthy subjects completed a functional MRI paradigm of right finger abduction with four stages; light resistance, strong resistance, imagined movement and attempted abduction after ulnar nerve blockade. Activation maps compared images acquired during rest and task, while region of interest analysis measured numbers of activated pixels. RESULTS: All subjects showed some ipsilateral SMC activation. Across all subjects and all tasks involving hand movement, contralateral activation was proportional to ipsilateral activation (2.1:1; r=0.86). CONCLUSIONS: The relationship between ipsilateral and contralateral SMC activation remained stable despite differing effort or hand paralysis. The contralateral and ipsilateral SMC appear to act in a coordinated fashion during unilateral hand movements.

Adult↗