Philip A. Boulby

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 Brocas and Wernickes 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.

Combined functional MRI and tractography to demonstrate the connectivity of the human primary motor cortex in vivo.

In this study, we combined advanced MR techniques to explore primary motor cortex (M1) connectivity in the human brain. We matched functional and anatomical information using motor functional MRI (fMRI) and white matter tractography inferred from diffusion tensor imaging (DTI). We performed coregistered DTI and motor task fMRI in 8 right-handed healthy subjects and in 1 right-handed patient presenting with a left precentral tumour. We used the fast-marching tractography (FMT) algorithm to define 3D connectivity maps within the whole brain, from seed points selected in the white matter adjacent to the location of the maximum of fMRI activation. Connectivity maps were then anatomically normalised and analysed using statistical parametric mapping software (SPM99) allowing group comparisons (left versus right hemisphere in control subjects and patient versus control subjects). The results demonstrated, in all control subjects, strong connections from M1 to the pyramidal tracts, premotor areas, parietal cortices, thalamus, and cerebellum. M1 connectivity was asymmetric, being more extensive in the dominant hemisphere. The patient had differences in M1 connectivity from the control group. Thus, fMRI-correlated DTI-FMT is a promising tool to study the structural basis of functional networks in the human brain in vivo.

Reorganization of verbal and nonverbal memory in temporal lobe epilepsy due to unilateral hippocampal sclerosis

Summary:  Purpose: Patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) often suffer from material‐specific memory impairments. The purpose of this study was to use functional magnetic resonance imaging (fMRI) to study the organization of specific memory functions in these patients.

Preoperative fMRI predicts memory decline following anterior temporal lobe resection

Background: Anterior temporal lobe resection (ATLR) benefits many patients with refractory temporal lobe epilepsy (TLE) but may be complicated by material specific memory impairments, typically of verbal memory following left ATLR, and non-verbal memory following right ATLR. Preoperative memory functional MRI (fMRI) may help in the prediction of these deficits. Objective: To assess the value of preoperative fMRI in the prediction of material specific memory deficits following both left- and right-sided ATLR. Methods: We report 15 patients with unilateral TLE undergoing ATLR; eight underwent dominant hemisphere ATLR and seven non-dominant ATLR. Patients performed an fMRI memory paradigm which examined the encoding of words, pictures and faces. Results: Individual patients with relatively greater ipsilateral compared with contralateral medial temporal lobe activation had greater memory decline following ATLR. This was the case for both verbal memory decline following dominant ATLR and for non-verbal memory decline following non-dominant ATLR. For verbal memory decline, activation within the dominant hippocampus was predictive of postoperative memory change whereas activation in the non-dominant hippocampus was not. Conclusion: These findings suggest that preoperative memory fMRI may be a useful non-invasive predictor of postoperative memory change following ATLR and provide support for the functional adequacy theory of hippocampal function. They also suggest that fMRI may provide additional information, over that provided by neuropsychology, for use in the prediction of postoperative memory decline.

Optimal acquisition orders of diffusion‐weighted MRI measurements

To propose a new method to optimize the ordering of gradient directions in diffusion‐weighted MRI so that partial scans have the best spherical coverage.

MR tractography predicts visual field defects following temporal lobe resection

A superior homonymous quadrantanopia is a well recognized complication of anterior temporal lobe resection and occurs because of disruption of the Meyer loop, the anterior part of the optic radiation. The authors used diffusion tensor imaging tractography to visualize the optic radiation before and after surgery, demonstrating the disruption of Meyer loop in a patient who developed a quadrantanopia. Preoperative imaging of the optic radiation will be useful in predicting visual field defects following temporal lobe resection.

Noninvasive in vivo demonstration of the connections of the human parahippocampal gyrus

MR tractography techniques provide a method for noninvasively studying white matter pathways in vivo. In this study we have used diffusion tensor imaging (DTI) and the fast marching tractography (FMT) algorithm to plot the structural connectivity of the human parahippocampal gyrus (PHG) in 10 healthy subjects, using seed points selected in the anterior parahippocampal gyrus. Our results demonstrate connectivity between the parahippocampal gyrus and the anterior temporal lobe, orbitofrontal areas, posterior temporal lobe and extrastriate occipital lobe via the lingual and fusiform gyri. We also demonstrate for the first time noninvasively direct connectivity between the parahippocampal gyrus and the hippocampus itself. These results agree with previous histological tract-tracing studies in animals. The connections demonstrated between neocortical areas and the hippocampus via the parahippocampal gyrus may provide the structural basis for theoretical models of memory and higher visual processing.

Material-specific lateralization of memory encoding in the medial temporal lobe: Blocked versus event-related design

Lesion-deficit studies have provided evidence for a functional dissociation between the left medial temporal lobe (MTL) mediating verbal memory encoding and right MTL mediating non-verbal memory encoding. While a small number of functional MRI studies have demonstrated similar findings, none has looked specifically for material-specific lateralization using subsequent memory effects. In addition, in many fMRI studies, encoding activity has been located in posterior MTL structures, at odds with lesion-deficit and positron emission tomography (PET) evidence. In this study, we used an event-related fMRI memory encoding paradigm to demonstrate a material-specific lateralization of encoding in the medial temporal lobes of ten healthy control subjects. Activation was left-lateralized for word encoding, bilateral for picture encoding, and right-lateralized for face encoding. Secondly, we demonstrated the locations of activations revealed using an event-related analysis to be more anterior than those revealed using a blocked analysis of the same data. This suggests that anterior MTL structures underlie memory encoding as judged by subsequent memory effects, and that more posterior activity detected in other fMRI studies is related to deficiencies of blocked designs in the analysis of memory encoding.

Tractography of the parahippocampal gyrus and material specific memory impairment in unilateral temporal lobe epilepsy

Introduction Temporal lobe epilepsy (TLE) is associated with disrupted memory function. The structural changes underlying this memory impairment have not been demonstrated previously with tractography. Methods We performed a tractography analysis of diffusion magnetic resonance imaging scans in 18 patients with unilateral TLE undergoing presurgical evaluation, and in 10 healthy controls. A seed region in the anterior parahippocampal gyrus was selected from which to trace the white matter connections of the medial temporal lobe. A correlation analysis was carried out between volume and mean fractional anisotropy (FA) of the connections, and pre-operative material specific memory performance. Results There was no significant difference between the left and right sided connections in controls. In the left TLE patients, the connected regions ipsilateral to the epileptogenic region were found to be significantly reduced in volume and mean FA compared with the contralateral region, and left-sided connections in control subjects. Significant correlations were found in left TLE patients between left and right FA, and verbal and non-verbal memory respectively. Conclusion Tractography demonstrated the alteration of white matter pathways that may underlie impaired memory function in TLE. A detailed knowledge of the integrity of these connections may be useful in predicting memory decline in chronic temporal lobe epilepsy.

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.