Browsing by Author "Du Plessis, Lindie"

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    An investigation of the integrity of two components of the cerebellar neurocircuitry involved in classical eyeblink conditioning in children prenatally exposed to alcohol: a magnetic resonance spectroscopy and functional magnetic resonance imaging study
    (2014) Du Plessis, Lindie; Meintjes, Ernesta
    Impairment in classical eyeblink conditioning (EBC) has previously been reported in children with fetal alcohol spectrum disorders (FASD) (Jacobson et al., 2008). The deep cerebellar nuclei and cerebellar cortex are critical elements of the cerebellar-brainstem circuitry that mediates EBC (Green et al., 2002a; Yeo and Hardiman, 1992; Perret et al., 1993). In this study, we used magnetic resonance spectroscopy (MRS) and functional MRI (fMRI) to assess the effects of prenatal alcohol exposure on brain metabolism in the cerebellar deep nuclei and brain function in the cerebellar cortex, respectively. We found that higher levels of prenatal alcohol exposure were associated with lower levels of both N-Acetylaspartate (NAA) and choline-containing metabolites, and with higher levels of glutamate plus glutamine (Glx), suggesting a disruption of the glutamate-glutamine cycling involved in glutamatergic excitatory neurotransmission. Since the interpositus nucleus is one of the most crucial structures in the acquisition of the EBC response, abnormal metabolism in this region could be responsible for altered synaptic plasticity in children with FASD. Of the four cerebellar regions that were identified as being activated more by control children during rhythmic vs. non-rhythmic finger tapping, smaller differences in BOLD (blood oxygenation level dependent) activation were observed in children with FASD in two, namely vermis IV-V and right Crus I. Increasing levels of prenatal alcohol exposure were, however, associated with smaller differences in activation in all four regions, all of which have previously been linked to timed responses. In the paced/unpaced finger tapping fMRI study, we found four regions where increased BOLD activation during unpaced tapping compared to rest was associated with improved ability to maintain rhythm as evidenced by lower intertapping variability - right VIIIa and b, left VIIIa and right VI. These regions have previously been implicated in motor control with additional evidence of timing in lobule VI. In three of the regions, all except right VIIIa, increasing alcohol exposure was related to smaller increases in activation during unpaced tapping, with the strongest relations seen in the dosage dependent variable. Interestingly, the location of the activation in right VI is similar to a region that has been implicated in studies of EBC (Blaxton et al., 1996; Cheng et al., 2008). Our results point to altered metabolic levels in the deep nuclei and reduced functioning of several cerebellar cortical regions in children with FASD, highlighting the extensive damage caused by prenatal alcohol exposure. Although we did not find associations of EBC performance with either metabolite levels or activity in these regions, suggesting that damage to these areas are not primarily responsible for the observed EBC deficit, the extent of this damage could play a role in the impaired EBC performance seen in these children.
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    Magnetic resonance spectroscopy quality assessment at CUBIC and application to the study of the cerebellar deep nuclei in children with fetal alcohol spectrum disorder
    (2010) Du Plessis, Lindie; Meintjies, Ernesta
    In vivo magnetic resonance spectroscopy (MRS) is an imaging technique that allows the chemical study of human tissue non-invasively. The method holds great promise as a diagnostic tool once its reliability has been established. Inter-scanner variability has, however, hampered this from happening as results cannot easily be compared if acquired on different scanners. In this study a phantom was constructed to determine the localisation efficiency of the 3 T Siemens Allegra MRI scanner located at the Cape Universities Brain Imaging Centre (CUBIC). Sufficient localisation is the key to acquiring useful spectroscopic data as only the signal from a small volume of interest (VOI) is typically acquired. The phantom consisted of a Perspex cube located inside a larger Perspex sphere. Solutions of the cerebral metabolites N-acetyl aspartate (NAA) and choline (Cho) were placed in the inner cube and outer sphere respectively. The phantom was scanned at a range of voxel sizes and echo times in order to determine parameters that typically indicate the performance of the scanner in question. The resultant full width at half maximum (FWHM) and signal to noise ratio (SNR) values indicated that optimal results were obtained for a voxel with dimensions 20 x 20 x 20 mm3. The selection efficiency could not be measured due to limitations in the scanner, but two other performance parameters ' extra volume suppression (EVS) and contamination ' could be determined. The EVS showed that the scanner was able to eliminate the entire background signal from the out-of-voxel region when voxel sizes with dimensions (20 mm)3 and (30 mm)3 were used. This performance decreased to 96.2% for a voxel size of (50 mm)3. The contamination indicated that the unwanted signal, weighted by the respective proton densities of the chemicals, ranged from 12% in the (20 mm)3 voxel to 24% in the (50 mm)3 voxel. These ranges are well within acceptable limits for proton MRS. Analysis of the water suppression achieved in the scanner showed an efficiency of 98.84%, which is acceptable for proton spectroscopy. It was also found that manual iv shimming of the scanner improved the spectra obtained, as compared to the automated shimming performed by the scanner. The second objective of the study was to quantify absolute metabolite concentrations in the familiar SI units of mM as results were previously mostly expressed as metabolite ratios. The LCModel software was used to assess two methods of determining absolute metabolite concentrations and the procedure using water scaling consistently showed superior performance to a method using a calibration factor. The method employing water scaling was then applied to a study of fetal alcohol spectrum disorder (FASD) where the deep cerebellar nuclei of children with FASD and a control group were scanned. The cerebellar nuclei were of interest as children with FASD show a remarkably consistent deficit in eye blink conditioning (EBC). The cerebellar deep nuclei is known to play a critical role in the EBC response. The results show significant decreases in the myo-inositol (mI) and total choline (tCho) concentrations of children with FASD in the deep cerebellar nuclei compared to control children. The FAS/PFAS subjects have a mean mI concentration of 4.6 mM as compared to a mean of 5.3 mM in the controls. A Pearson correlation showed that there was a significant relationship between decreasing mI concentrations with increasing prenatal alcohol exposure. The mean tCho concentrations are 1.3 mM for FAS/PFAS and 1.5 mM for the controls. There was no significant differences between the heavily exposed group and either the FAS/PFAS or the control subjects for either metabolite. The decreased mI and tCho concentrations may indicate deficient calcium signalling or decreased cell membrane integrity ' both of which can explain the compromised cerebellar learning in FASD subjects.