Browsing by Author "Taylor, Paul A"

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    Differences in resting state functional networks in HIV infected and uninfected children at age 7 years
    (2015) Toich, Jadrana; Meintjes, Ernesta M; Holmes, Martha; Taylor, Paul A
    Although early administration of highly active antiretroviral therapy (HAART) in infants provides the brain some protection against HIV damage, few studies have examined the long-term effects of HIV infection and HAART on neurodevelopment, and none have measured their impact on functional brain networks in young children. We use resting state functional magnetic resonance imaging (RS-fMRI) to explore differences in functional connectivity (FC) in HIV infected children stable on HAART and in HIV uninfected children. The 9 resting state networks (RSNs) identified using independent component analysis (ICA) included the visual lingual gyrus, visual occipital gyrus, salience, dorsal attention, auditory, motor, executive control, posterior default mode network (pDMN) and default mode network (DMN) . No significant group level differences were found in any RSNs using ICA. However, seed-based correlation analysis ( SCA ) revealed two regions where uninfected children had a higher FC compared to infected children (p < 0. 05 corrected for multiple comparison); specifically, between a seed in the left cingulate gyrus of the DMN and the left middle frontal gyrus, and between a seed in the right middle frontal gyrus of the executive control network and the right supramarginal gyrus. Consistent with our findings, previous RS-fMRI studies in HIV infected adults have reported reduced connectivity compared to uninfected adults in numerous DMN regions and executive control network. However, in contrast to the adult literature, in which a number of areas within the networks have been implicated, we only observed a focal effect in each of the two RSNs. Given that some of the RSNs are still undergoing major developments at age 7 years (i.e . time of scan for the children), the reduced FC may represent delayed network maturation within the infected cohort , with potential effects on cognitive functioning, information processing and memory recall abilities . Furthermore, positive associations were found between the clinical CD4/CD8 at time of enrollment and two regions within the dorsal attention and auditory networks. These results were independent of treatment arm and suggest that reduced FC in these networks at age 7 years are a result of poor immune function in early infancy (6-8 weeks of age), supporting the notion of in itiating ART immediately in HIV infected infants.
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    Neuroimaging study of prenatal alcohol exposure effects on structural and functional connectivity in children
    (2015) Fan, Jia; Meintjes, Ernesta M; Taylor, Paul A
    Fetal alcohol spectrum disorders (FASD) describe the spectrum of cognitive, behavioural and neurological impairments associated with prenatal alcohol exposure (PAE). Diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) were used to assess effects of PAE on microstructural integrities of cerebellar and cerebral white matters (WM) and on resting-state functional connectivity (RSFC) in gray matter (GM) in children with varying degrees of FASD severity (fetal alcohol syndrome (FAS) and partial FAS (PFAS)), as well as nonsyndromal heavily exposed (HE) children. Children with FAS revealed lower fractional anisotropy (FA) bilaterally in the superior peduncles. Mean diffusivity (MD) was higher in the left middle peduncle in children with FAS or PFAS (FAS/PFAS). Mediation of effects of PAE on eyeblink conditioning (EBC) provided statistical evidence that poorer microstructural integrity in these regions may play an important role in the EBC deficit observed in children with FASD. The FAS/PFAS children also revealed lower FA and/or higher MD in 7 cortical WM regions and lower RSFC in 5 GM regions within 5 networks. Four of the 7 WM and 3 of the 5 GM regions also showed alterations in HE children, providing evidence that alterations in nonsyndromal children are less extensive and that some regions appear to be relatively spared. Alterations in DTI parameters (FA and MD) were dose dependent in many, but not all, of the regions where group differences were detected, specifically in the left (L) and right (R) superior peduncles, L middle peduncle, L inferior longitudinal fasciculus, medial (M) splenium of the corpus callosum (CC), and M isthmus of the CC. The WM deficits were attributable to increased radial diffusivity (RD) rather than decreased axial diffusivity (AD), suggesting poorer axon packing density and/or myelination. Increasing alcohol exposure was associated with reduced fractional amplitude of low frequency fluctuations (fALFF), indicating changes in functional connectivity in the default mode, salience, and dorsal attention networks. The locations of the WM alterations found with DTI suggest that the compromised RSFC found in 3 of the 5 networks could be attributable to WM deficits in tracts providing intra-network connections.
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    Simultaneous DTI and rs-fMRI using the navigated diffusion sequence
    (2016) Mofya, Mwape; Meintjes, Ernesta M; Alhamud, Alkathafi Ali; Taylor, Paul A
    Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) experiments are normally performed separately. The idea of extracting inherently co-registered activation/connectivity maps and diffusion parameters has resulted in efforts to develop methods for simultaneous fMRI and DTI data acquisition. Recently, a 3D echo planar imaging (EPI) acquisition was successfully inserted after each DTI volume to perform real-time motion correction, with the two sequence protocols remaining separate. We examined using a single 3D EPI acquisition, inserted following each DTI volume acquisition (hereafter called the single nav sequence), modified to acquire BOLD resting state fMRI (rs-fMRI) data. We also investigated inserting a second 3D EPI acquisition in the middle of each DTI volume acquisition (hereafter called the double nav sequence) to increase fMRI temporal resolution. Two adult subjects were scanned with the navigated sequences and the standard separate 2D EPI BOLD and DTI acquisitions for comparison. Preprocessing and analysis of data was performed using FATCAT, AFNI , FSL and in-house Python scripts. Four standard resting state networks (RSNs) were visually identified using the navigated diffusion sequences. While RSNs were apparent in the single nav case, they were quite noisy and in some cases entire regions did not show connectivity. The double nav connectivity maps were more similar to the standard BOLD connectivity maps in terms of the spatial extent of the regions showing connectivity to the seed. The whole brain distributions of fractional anisotropy (FA) and mean diffusivity (MD) were similar among the different acquisition protocols. The jackknife standard error was comparable between the navigated and standard protocols. Further comparisons of diffusion data made using probabilistic tractography and connectivity matrices showed overall small differences indicating that connections derived from the standard DTI, single nav and double nav protocols were overall similar. We have therefore shown a significant "proof of concept" of successfully acquiring simultaneous DTI and rs-fMRI data, and therefore for investigating brain structural and functional connectivity simultaneously.