Functional Connectivity Network Disruption Underlies Domain-Specific Impairments in Attention for Children Born Very Preterm.

Attention problems are common in school-age children born very preterm (VPT; < 32 weeks gestational age), but the contribution of aberrant functional brain connectivity to these problems is not known. As part of a prospective longitudinal study, brain functional connectivity (fc) was assessed alongside behavioral measures of selective, sustained, and executive attention in 58 VPT and 65 full-term (FT) born children at corrected-age 12 years. VPT children had poorer sustained, shifting, and divided attention than FT children. Within the VPT group, poorer attention scores were associated with between-network connectivity in ventral attention, visual, and subcortical networks, whereas between-network connectivity in the frontoparietal, cingulo-opercular, dorsal attention, salience and motor networks was associated with attention functioning in FT children. Network-level differences were also evident between VPT and FT children in specific attention domains. Findings contribute to our understanding of fc networks that potentially underlie typical attention development and suggest an alternative network architecture may help support attention in VPT children.

Altered functional network connectivity relates to motor development in children born very preterm.

Individuals born very preterm (<32 weeks gestation) are at increased risk for neuromotor impairments. The ability to characterize the structural and functional mechanisms underlying these impairments remains limited using existing neuroimaging techniques. Resting state-functional magnetic resonance imaging (rs-fMRI) holds promise for defining the functional network architecture of the developing brain in relation to typical and aberrant neurodevelopment. In 58 very preterm and 65 term-born children studied from birth to age 12 years, we examined relations between functional connectivity measures from low-motion rs-fMRI data and motor skills assessed using the Movement Assessment Battery for Children, 2nd edition. Across all subscales, motor performance was better in term than very preterm children. Examination of relations between functional connectivity and motor measures using enrichment analysis revealed between-group differences within cerebellar, frontoparietal, and default mode networks, and between basal ganglia-motor, thalamus-motor, basal ganglia-auditory, and dorsal attention-default mode networks. Specifically, very preterm children exhibited weaker associations between motor scores and thalamus-motor and basal ganglia-motor network connectivity. These findings highlight key functional brain systems underlying motor development. They also demonstrate persisting developmental effects of preterm birth on functional connectivity and motor performance in childhood, providing evidence for an alternative network architecture supporting motor function in preterm children.

MRI artefact in the rectum caused by ingested orthodontic brackets.

Magnetic susceptibility artefacts, caused by metallic objects, present a challenge in magnetic resonance imaging (MRI). In this case, MRI showed metal-induced artefact in the rectum of a 14-year-old girl who presented with pain in the coccyx after a snowboarding accident. Previous radiographs showed no evidence of metal in the area. After the identification of the artefact and upon discussion with the patient, she disclosed that two orthodontic brackets had been swallowed two days prior to the MRI examination, likely the source of artefact. Following the passage of the brackets, subsequent MRI was artefact-free. A similar artefact was recreated by scanning a potato with and without an orthodontic bracket, highlighting the impact of the resulting artefact on MRI.

The MoCA: well-suited screen for cognitive impairment in Parkinson disease.

OBJECTIVE: To establish the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) when screening externally validated cognition in Parkinson disease (PD), by comparison with a PD-focused test (Scales for Outcomes in Parkinson disease-Cognition [SCOPA-COG]) and the standardized Mini-Mental State Examination (S-MMSE) as benchmarks. METHODS: A convenience sample of 114 patients with idiopathic PD and 47 healthy controls was examined in a movement disorders center. The 21 patients with dementia (PD-D) were diagnosed using Movement Disorders Society criteria, externally validated by detailed independent functional and neuropsychological tests. The 21 patients with mild cognitive impairment (PD-MCI) scored 1.5 SD or more below normative data in at least 2 measures in 1 of 4 cognitive domains. Other patients had normal cognition (PD-N). RESULTS: Primary outcomes using receiver operating characteristic (ROC) curve analyses showed that all 3 mental status tests produced excellent discrimination of PD-D from patients without dementia (area under the curve [AUC], 87%-91%) and PD-MCI from PD-N patients (AUC, 78%-90%), but the MoCA was generally better suited across both assessments. The optimal MoCA screening cutoffs were <21/30 for PD-D (sensitivity 81%; specificity 95%; negative predictive value [NPV] 92%) and <26/30 for PD-MCI (sensitivity 90%; specificity 75%; NPV 95%). Further support that the MoCA is at least equivalent to the SCOPA-COG, and superior to the S-MMSE, came from the simultaneous classification of the 3 PD patient groups (volumes under a 3-dimensional ROC surface, chance = 17%: MoCA 79%, confidence interval [CI] 70%-89%; SCOPA-COG 74%, CI 62%-86%; MMSE-Sevens item 56%, CI 44%-68%; MMSE-World item 62%, CI 50%-73%). CONCLUSIONS: The MoCA is a suitably accurate, brief test when screening all levels of cognition in PD.

Host Cell Preference of Toxoplasma gondii Cysts in Murine Brain: A Confocal Study.

Toxoplasma gondii is a protozoan parasite that is widely prevalent in humans and typically results in a chronic infection characterized by cysts located predominantly in the central nervous system. In immunosuppressed hosts, such as patients with HIV infection, the infection can be reactivated from the cysts in the brain resulting in a severe and potentially fatal encephalitis. Studies suggest that the chronic infection may also have neuropathological and behavioral effects in immune competent hosts. An improved understanding of tissue cyst behavior is of importance for understanding both the reactivation as well as the neurophysiological consequences of chronic infection. In vivo studies have identified neurons as host cells for cysts but in vitro studies have found that astrocytes can also foster development of the cysts. In this study we have addressed the question of which neural cell tissue cysts of T. gondii reside during chronic infection using a mouse model. Mice were infected with Me49 Strain T. gondii and the intracellular localization of the cysts analyzed during the development and establishment of a chronic infection at 1, 2, and 6 months post infection. Brains were fixed, cryosectioned, and stained with FITC-Dolichos biflorans to identify the Toxoplasma cysts and they were labeled with cell specific antibodies to neurons or astrocytes and then analyzed using confocal fluorescence microscopy. Cysts were found to occur almost exclusively in neurons throughout chronic infection. No cysts were identified in astrocytes, using the astrocyte marker, GFAP. Astrocyte interactions with neuronal-cysts, however, were frequently observed.

The gamma interferon (IFN-gamma)-inducible GTP-binding protein IGTP is necessary for toxoplasma vacuolar disruption and induces parasite egression in IFN-gamma-stimulated astrocytes.

Toxoplasma gondii is a common central nervous system infection in individuals with immunocompromised immune systems, such as AIDS patients. Gamma interferon (IFN-gamma) is the main cytokine mediating protection against T. gondii. Our previous studies found that IFN-gamma significantly inhibits T. gondii in astrocytes via an IFN-gamma-inducible GTP-binding protein (IGTP)-dependent mechanism. The IGTP-dependent-, IFN-gamma-stimulated inhibition is not understood, but recent studies found that IGTP induces disruption of the parasitophorous vacuole (PV) in macrophages. In the current study, we have further investigated the mechanism of IFN-gamma inhibition and the role of IGTP in the vacuolar disruption in murine astrocytes. Vacuolar disruption was found to be dependent upon IGTP, as PV disruption was not observed in IGTP-deficient (IGTP(-/-)) astrocytes and PV disruption could be induced in IGTP(-/-) astrocytes transfected with IGTP. Live-cell imaging studies using green fluorescent protein-IGTP found that IGTP is delivered to the PV via the host cell endoplasmic reticulum (ER) early after invasion and that IGTP condenses into vesicle-like structures on the vacuole just prior to PV disruption, suggesting that IGTP is involved in PV disruption. Intravacuolar movement of the parasite occurred just prior to PV disruption. In some instances, IFN-gamma induced parasite egression. Electron microscopy and immunofluorescence studies indicate that the host cell ER fuses with the PV prior to vacuolar disruption. On the basis of these results, we postulate a mechanism by which ER/PV fusion is a crucial event in PV disruption. Fusion of the ER with the PV, releasing calcium into the vacuole, may also be the mechanism by which intravacuolar parasite movement and IFN-gamma-induced parasite egression occur.

Spectroscopic biomedical imaging with the Medipix2 detector.

This study confirms that the Medipix2 x-ray detector enables spectroscopic bio-medical plain radiography. We show that the detector has the potential to provide new, useful information beyond the limited spectroscopic information of modem dual-energy computed tomography (CT) scanners. Full spectroscopic 3D-imaging is likely to be the next major technological advance in computed tomography, moving the modality towards molecular imaging applications. This paper focuses on the enabling technology which allows spectroscopic data collection and why this information is useful. In this preliminary study we acquired the first spectroscopic images of human tissue and other biological samples obtained using the Medipix2 detector. The images presented here include the clear resolution of the 1.4mm long distal phalanx of a 20-week-old miscarried foetus, showing clear energy-dependent variations. The opportunities for further research using the forthcoming Medipix3 detector are discussed and a prototype spectroscopic CT scanner (MARS, Medipix All Resolution System) is briefly described.