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Biomedical subjects

Mark P Richardson

Publications and source records attributed to Mark P Richardson.

13 recordsLinked to original sources

BOLD correlates of EMG spectral density in cortical myoclonus: description of method and case report.

The recording of electrophysiological data during BOLD fMRI is highly challenging but provides the opportunity to develop a more thorough account of brain function than either modality alone. To develop new techniques in this area has often required the study of pathological electrophysiological measures because such measures can be unusually strong (e.g., epileptic EEG spikes) and hence more easily detectable during fMRI than weaker normal phenomena. In this paper, we have studied pathologically strong EMG signals in a patient with cortical myoclonus. First, we studied the patient outside of scanning: The pathological corticospinal drive to muscle was concentrated over 6-30 Hz so that EMG components at higher frequency could be used to control for non-corticospinal contributions to the EMG during scanning. Additionally, there was very strong EMG-EMG and EMG-EEG coherence in this frequency band. Furthermore, analysis of spectral phase showed that this exaggerated coherence was produced by efferent drive from brain to muscle. Hence, the exaggerated peak in distal muscle EMG power spectrum reflected brain activity producing the efferent drive. Subsequently, we modified equipment and data analysis techniques previously developed for simultaneous EEG-fMRI to record polychannel EMG from distal upper limbs during simultaneous BOLD fMRI. After artefact reduction, the EMG recorded during fMRI retained the essential frequency and phase characteristics of EMG recorded outside of scanning. The BOLD signal was significantly correlated with time-varying 6- to 30-Hz power in a frontoparietal network compatible with the neurophysiological characteristics of our patient and compatible with prior hypotheses explaining the origin of cortical myoclonus.

Adult↗

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↗

Distant influences of amygdala lesion on visual cortical activation during emotional face processing.

Emotional visual stimuli evoke enhanced responses in the visual cortex. To test whether this reflects modulatory influences from the amygdala on sensory processing, we used event-related functional magnetic resonance imaging (fMRI) in human patients with medial temporal lobe sclerosis. Twenty-six patients with lesions in the amygdala, the hippocampus or both, plus 13 matched healthy controls, were shown pictures of fearful or neutral faces in task-releant or task-irrelevant positions on the display. All subjects showed increased fusiform cortex activation when the faces were in task-relevant positions. Both healthy individuals and those with hippocampal damage showed increased activation in the fusiform and occipital cortex when they were shown fearful faces, but this was not the case for individuals with damage to the amygdala, even though visual areas were structurally intact. The distant influence of the amygdala was also evidenced by the parametric relationship between amygdala damage and the level of emotional activation in the fusiform cortex. Our data show that combining the fMRI and lesion approaches can help reveal the source of functional modulatory influences between distant but interconnected brain regions.

Adult↗

Pre-operative verbal memory fMRI predicts post-operative memory decline after left temporal lobe resection.

Functional MRI (fMRI) of cognitive tasks depends on technology widely available in the clinical sphere, but has yet to show a role in the investigation of patients. We report here the first demonstration of a clinically valuable role for cognitive fMRI. Temporal lobe epilepsy (TLE) is commonly caused by hippocampal sclerosis and is frequently resistant to drug treatment. Surgical resection of the left hippocampus in this setting can cure seizures, but may produce significant verbal memory decline, which is hard to predict. We report 10 right-handed TLE patients with left hippocampal sclerosis who underwent left hippocampal resection. We compared currently used data for the prediction of post-operative verbal memory decline in such patients with a novel fMRI assessment of verbal memory encoding. Multiple regression analyses showed that fMRI provided the strongest independent predictor of memory outcome after surgery. At the individual subject level, the fMRI data had high positive predictive value for memory decline.

Adult↗

Encoding of emotional memories depends on amygdala and hippocampus and their interactions.

We have studied patients with variable degrees of left hippocampal and amygdala pathology who performed a verbal encoding task during functional magnetic resonance imaging (fMRI) to assess the impact of pathology on emotional-memory performance and encoding-evoked activity. The severity of left hippocampal pathology predicted memory performance for neutral and emotional items alike, whereas the severity of amygdala pathology predicted memory performance for emotional items alone. Encoding-related hippocampal activity for successfully remembered emotional items correlated with the degree of left amygdala pathology. Conversely, amygdala-evoked activity with respect to subsequently remembered emotional items correlated with the degree of left hippocampal pathology. Our data indicate a reciprocal dependence between amygdala and hippocampus during the encoding of emotional memories.

Adolescent↗

The application of functional MRI of memory in temporal lobe epilepsy: a clinical review.

Functional MRI (fMRI) is a useful tool for noninvasively localizing areas in the brain involved in specific cognitive functions. Since its introduction, there has been considerable speculation regarding the role it may play in the presurgical assessment of temporal lobe epilepsy (TLE). This review considers the progress made to date in using fMRI to investigate memory processing in the medial temporal lobe in normal subjects and in those with TLE. Results so far suggest that fMRI will be incorporated into the presurgical assessment of TLE in the coming years to improve definition of eloquent cerebral areas, with the objective of minimizing the adverse cognitive sequelae of anterior temporal lobe resection.

Brain Mapping↗

Preserved verbal memory function in left medial temporal pathology involves reorganisation of function to right medial temporal lobe.

The left hippocampus and related structures mediate verbal memory function. The mechanism underlying preserved verbal memory function in patients with left hippocampal damage is unknown. Temporal lobe epilepsy, a common disease, is frequently the consequence of a characteristic hippocampal pathology termed hippocampal sclerosis, which may also affect the amygdala. In this setting, mapping the sites of memory function is a vital component of planning for surgical treatment for epilepsy. Using event-related functional magnetic resonance imaging, we studied 24 right-handed nonamnesic patients with left hippocampal sclerosis and 12 normal controls, performing a verbal encoding task. The patients were subdivided into two groups according to presence or absence of additional left amygdala pathology. Analysis of the data employed a two-level random-effects design, examining the main effects of subsequent memory in each group, as well as the differences between the groups. Additional effects of emotionality of the remembered words were also examined. Verbal memory encoding involved activation of left hippocampus in normals, but was associated with reorganisation to right hippocampus and parahippocampal gyrus in the patients. The additional presence of left amygdala sclerosis resulted in reorganisation for encoding of emotional verbal material to right amygdala. Retained verbal memory function in the presence of left medial temporal lobe pathology is mediated by recruitment of a parallel system in the right hemisphere consistent with adaptive functional reorganisation. The findings indicate a high degree of plasticity in medial temporal lobe structures.

Amygdala↗

Epilepsy and surgical mapping.

Drug treatment resistant epilepsy is an important public health problem. Patients with epilepsy of focal origin may have an excellent outcome following surgery that removes the source of seizures. Identification of the precise cortical region producing seizures is crucial to a good outcome; additionally, identification of eloquent cortical areas near the region to be resected is essential to prevent postoperative neurological deficit. A wide range of imaging techniques is valuable for imaging the epileptogenic zone, including high-resolution T1 MRI, T2 signal quantitation, MR spectroscopy, diffusion imaging, PET, SPECT and simultaneous EEG-fMRI. Eloquent cortex has in the past been mapped using highly invasive techniques; fMRI of motor and cognitive tasks holds great promise for future non-invasive mapping strategies.

Brain↗

Grey and white matter flumazenil binding in neocortical epilepsy with normal MRI. A PET study of 44 patients.

In 20-30% of potential surgical candidates with refractory focal epilepsy, standard MRI does not identify the cause. gamma-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. [(11)C]Flumazenil (FMZ) PET images most subtypes of GABA(A) receptors, present on most neurons. We investigated [(11)C]FMZ binding in grey and white matter in 16 normal controls and in 44 patients with refractory neocortical focal epilepsy and normal optimal MRI. Fourteen patients had unilateral frontal lobe epilepsy, five occipital lobe epilepsy (OLE), six parietal lobe epilepsy (PLE) and 19 neocortical epilepsy that was not clearly lobar. Parametric images of FMZ volume of distribution (FMZ-V(d)) were computed. Statistical parametric mapping (SPM99) with explicit masking, including the white matter, was used to analyse individual patients and groups. Thirty-three of the 44 patients showed focal abnormal FMZ-V(d); increases in 16, decreases in eight, and both increases and decreases in nine. In seven patients, the increases in FMZ binding were periventricular, in locations normally seen in periventricular nodular heterotopia on MRI. There were frontal and parietal increases in FMZ binding in grey and white matter in the PLE group and decreases in the cingulate gyrus in the OLE group. FMZ binding increases, particularly periventricular increases, were a prominent feature of MRI-negative focal epilepsies and may represent neuronal migration disturbances.

Adolescent↗

Implementation and application of a brain template for multiple volumes of interest.

We present a region template and a protocol for transforming that template to define anatomical volumes of interest (VOIs) in the human brain without operator intervention, based on software contained in the SPM99 package (Statistical Parametric Mapping, Wellcome Department of Cognitive Neurology, London, UK). We used an MRI of a reference brain to create an anatomical template of 41 VOIs, covering the entire brain, that can be spatially transformed to fit individual brain scans. Modified software allows for the reslicing and adaptation of the transformed template to any type of coregistered functional data. Individually defined VOIs can be added. We present an assessment of the necessary spatial transformations and compare results obtained for scans acquired in two different orientations. To evaluate the spatial transformations, 11 landmarks distributed throughout the brain were chosen. Euclidean distances between repeat samples at each landmark were averaged across all landmarks to give a mean difference of 1.3 plus minus 1.0 mm. Average Euclidean distances between landmarks (MRI:transformed template) were 8.1 plus minus 3.7 mm in anterior-posterior commissure (ACPC) and 7.6 plus minus 3.7 mm in temporal lobe (TL) orientation. In this study, we use [(11)C]-flumazenil-(FMZ-)PET as an example for the application of the region template. Thirty-four healthy volunteers were scanned, 21 in standard ACPC orientation, 13 in TL orientation. All had high resolution MRI and FMZ-PET. The average coefficient of variation (CV) of FMZ binding for cortical regions was 0.15, comparable with CVs from manually defined VOIs. FMZ binding was significantly different in 6/19 anatomical areas in the control groups obtained in the different orientations, probably due to anisotropic voxel dimensions. This new template allows for the reliable and fast definition of multiple VOIs. It can be used for different imaging modalities and in different orientations. It is necessary that imaging data for groups compared are acquired in the same orientation.

Adult↗

Functional imaging in epilepsy.

Functional imaging plays a growing role in the clinical assessment and research investigation of patients with epilepsy. This article reviews the literature on functional MRI (fMRI) investigation of EEG activity, fMRI evaluation of cognitive and motor functions, magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT) and positron emission tomography (PET) in epilepsy. The place of these techniques in clinical evaluation and their contribution to a better neurobiological understanding of epilepsy are discussed.

Anticonvulsants↗