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The UF was reconstructed using a two ROI approach to restrict fibre assignment to the UF (Figure 3.1). On the axial colourised FA map, a ROI was placed encompassing the perpendicular fibres passing through the temporal stem in the anterior temporal lobe towards the orbitofrontal cortex (Mori et al., 2005). A second ROI was placed in each patient on an inferior axial slice closer to the inferior and anterior portion of the temporal lobe, encompassing the fibres of the UF, in order to restrict fibre assignment to the UF. Fibres were reconstructed that passed through both ROIs. Fibre tracking was performed using the FACT algorithm (Mori et al., 1999; Stieltjes et al., 2001) implemented within the DTI task card software, as described in chapter 2. In this study, tracking was terminated when it reached a voxel with a FA lower than a threshold of 0.2 and when the

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angle between the two principal eigenvectors was greater than 50o. Both of these thresholds were user defined. Measures of FA and ADC were obtained for the entire reconstructed UF.

Figure 3.1 Reconstruction of the UF

A: The figure illustrates placement of the two ROIs to reconstruct the UF.

The white arrow shows the location of the fibres of the right UF in the axial slice of the colourised fibre orientation map. The ROI in orange on the left shows the superior of the two ROIs used to reconstruct the UF.

B: The reconstructed left UF is displayed from a left lateral angle. The two ROIs used for reconstruction are visible in orange and pink colour.

In order to gain insight into the underlying microstructural sources of the observed differences in the FA and ADC values measured for the tracts, the diffusion along each of the main three directions, i.e. eigenvalues (λ1, λ2, λ3) (mean ± SD), was examined along with the FA and ADC, for an ROI contained within the rostro- caudal course of the UF within the temporal stem. This ROI was selected after reconstruction of the UF to include only fibres that followed the course of the UF.

The axial and radial diffusivities were computed for each individual ROI within the UF in order to independently evaluate the degree of diffusion parallel and

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perpendicular to the UF tract at that location. Such measurements in the axial and perpendicular direction allow elucidation of the mechanism producing the observed changes in anisotropy, thus providing insights into the underlying pathology. Due to the non-linear trajectory of the white matter tracts, such estimates of axial and perpendicular diffusivities are only meaningful in one single plane and these changes were only reported for one ROI, contained within the UF. This region was located within the temporal stem, where the UF has a rostro caudal orientation and can be easily identified.

Figure 3.2 DTT of the UF

A: Sagittal and axial cuts of colourised fibre orientation map of a 34 years old woman with intractable left temporal neocortical epilepsy. The UF is displayed in yellow (left UF) and red (right UF).

- 61 - 3.2.3 Neuropsychological protocol

All TLE patients underwent a comprehensive neuropsychological evaluation as part of their pre-surgical investigations. The Wechsler Memory Scale – Third Edition (WMS-III) was administered as part of the neuropsychological battery. Four memory indices from the WMS-III were used in the current study to evaluate memory performance. The Auditory Immediate Memory Index and the Auditory Delayed Memory Index were used to assess verbal memory. The Visual Immediate Memory Index and the Visual Delayed Memory Index were used to assess visual memory.

3.2.4 Analyses

In order to compare age at seizure onset and duration of epilepsy in the TLE groups (left, right), U tests were computed.

To evaluate DTI measures, two-tailed t-tests were conducted to examine differences in FA and ADC between left and right UF among the study groups and differences in FA and ADC values between the groups. Then, Spearman correlations between DTI and memory measures in the TLE groups were examined. Given the exploratory nature of this study, no correction for Type I error was made.

To obtain measures of reliability, the UF was reconstructed in ten controls on both sides, on two separate occasions four months apart, by the same rater (BD) and reliability was assessed using Cronbach’s alpha values.

In all tests, statistical significance was set to P<0.05. All analyses were performed using the SPSS software package (SPSS, Chicago, IL).

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Demographics were comparable between the study groups and are shown in Table 3.1 (controls: age range 26-52, median 37; right TLE: range 28-55, median 39, mean 36.3+6.6 years; left TLE: range 24-47, median 36, mean 41.8+8.2 years). Specifically, no difference was found in age at onset of epilepsy in the left versus right TLE group (right TLE: median age at seizure onset 16.5 years, range 10-42; median duration of epilepsy 23 years, range 2-28; left TLE: median age at onset 23 years, range 5-42; median duration 22.5 years, range 1-41).

All controls and the majority of epilepsy patients were right-handed using the Edinburgh handedness questionnaire. A total of 10 patients were left-handed or ambidextrous. These patients were confirmed to be left hemisphere dominant for speech on Wada testing or functional MRI; therefore all subjects are likely to be left hemisphere dominant for language.

Table 3.1 Demographic and seizure data for study patients

Variable Left Temporal Right Temporal

Median (range) Median (range)

Age 36.00 (24-47) 39.00 (28-55)

Education 14.00 (12-19) 12.00 (8-17) Age of seizure onset 23.00 (5-42) 16.50 (10-42) Duration of Epilepsy 22.50 (1-41) 23.00 (2-28)

Sex Male = 5 (28%) Male = 6 (60%)

Female = 13 (72%) Female = 4 (40%) Race Caucasian = 18 (100%) Caucasian = 10 (100%)

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