Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.

The brain mechanisms of cognitive-behavioral therapy (CBT), a highly effective treatment for pediatric obsessive-compulsive disorder (OCD), are unknown. Neuroimaging in adult OCD indicates that CBT is associated with metabolic changes in striatum, thalamus, and anterior cingulate cortex. We therefore probed putative metabolic effects of CBT on these brain structures in pediatric OCD using proton magnetic resonance spectroscopic imaging (1H MRSI).

Previous quantitative synthetic MRI of the brain has been solely performed in 2D.

Interferon regulatory factor 2 binding protein-like (IRF2BPL) encodes a member of the IRF2BP family of transcriptional regulators. Currently the biological function of this gene is obscure, and the gene has not been associated with a Mendelian disease. Here we describe seven individuals who carry damaging heterozygous variants in IRF2BPL and are affected with neurological symptoms. Five individuals who carry IRF2BPL nonsense variants resulting in a premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, and a lack of coordination. Two additional individuals, both with missense variants, display global developmental delay and seizures and a relatively milder phenotype than those with nonsense alleles. The IRF2BPL bioinformatics signature based on population genomics is consistent with a gene that is intolerant to variation. We show that the fruit-fly IRF2BPL ortholog, called pits (protein interacting with Ttk69 and Sin3A), is broadly detected, including in the nervous system. Complete loss of pits is lethal early in development, whereas partial knockdown with RNA interference in neurons leads to neurodegeneration, revealing a requirement for this gene in proper neuronal function and maintenance. The identified IRF2BPL nonsense variants behave as severe loss-of-function alleles in this model organism, and ectopic expression of the missense variants leads to a range of phenotypes. Taken together, our results show that IRF2BPL and pits are required in the nervous system in humans and flies, and their loss leads to a range of neurological phenotypes in both species.

The domestic dog segregates a significant number of inherited progressive retinal diseases, several of which mirror human retinal diseases and which are collectively termed progressive retinal atrophy (PRA). In 2014, a novel form of PRA was reported in the Swedish Vallhund breed, and the disease was mapped to canine chromosome 17. The causal mutation was not identified, but expression analyses of the retinas of affected Vallhunds demonstrated a 6-fold increased expression of the MERTK gene compared to unaffected dogs. Using 24 retinopathy cases and 97 controls with no clinical signs of retinopathy, we replicated the chromosome 17 association in Swedish Vallhunds from the UK and aimed to elucidate the causal variant underlying this association using whole genome sequencing (WGS) of an affected dog. This revealed a 6-8 kb insertion in intron 1 of MERTK that was not present in WGS of 49 dogs of other breeds. Sequencing and BLASTN analysis of the inserted segment was consistent with the insertion comprising a full-length intact LINE-1 retroelement. Testing of the LINE-1 insertion for association with retinopathy in the UK set of 24 cases and 97 controls revealed a strong statistical association (P-value 6.0 x 10-11) that was subsequently replicated in the original Finnish study set (49 cases and 89 controls (P-value 4.3 x 10-19). In a pooled analysis of both studies (73 cases and 186 controls), the LINE-1 insertion was associated with a ~20-fold increased risk of retinopathy (odds ratio 23.41, 95% confidence intervals 10.99-49.86, P-value 1.3 x 10-27). Our study adds further support for regulatory disruption of MERTK in Swedish Vallhund retinopathy; however, further work is required to establish a functional overexpression model. Future work to characterise the mechanism by which this intronic mutation disrupts gene regulation will further improve the understanding of MERTK biology and its role in retinal function.

Differentiating WHO grade I-III of meningioma by non-invasive imaging is challenging. This study investigated the potential of MR arterial spin labeling (ASL) to establish tumor grade in meningioma patients.

The development of automatic methods for segmenting anatomy from medical images is an important goal for many medical and healthcare research areas. Datasets that can be used to train and test computer algorithms, however, are often small due to the difficulties in obtaining experts to segment enough examples. Citizen science provides a potential solution to this problem but the feasibility of using the public to identify and segment anatomy in a medical image has not been investigated. Our study therefore aimed to explore the feasibility, in terms of performance and motivation, of using citizens for such purposes. Public involvement was woven into the study design and evaluation. Twenty-nine citizens were recruited and, after brief training, asked to segment the spine from a dataset of 150 magnetic resonance images. Participants segmented as many images as they could within three one-hour sessions. Their accuracy was evaluated by comparing them, as individuals and as a combined consensus, to the segmentations of three experts. Questionnaires and a focus group were used to determine the citizens' motivation for taking part and their experience of the study. Citizen segmentation accuracy, in terms of agreement with the expert consensus segmentation, varied considerably between individual citizens. The citizen consensus, however, was close to the expert consensus, indicating that when pooled, citizens may be able to replace or supplement experts for generating large image datasets. Personal interest and a desire to help were the two most common reasons for taking part in the study.

Neurocognitive and psychiatric disorders have significant consequences for quality of life in patients with Parkinson's disease (PD). In the current study, we evaluated microstructural white matter (WM) alterations associated with neurocognitive and psychiatric disorders in PD using neurite orientation dispersion and density imaging (NODDI) and linked independent component analysis (LICA). The indices of NODDI were compared between 20 and 19 patients with PD with and without neurocognitive and psychiatric disorders, respectively, and 25 healthy controls using tract-based spatial statistics and tract-of-interest analyses. LICA was applied to model inter-subject variability across measures. A widespread reduction in axonal density (indexed by intracellular volume fraction [ICVF]) was demonstrated in PD patients with and without neurocognitive and psychiatric disorders, as compared with healthy controls. Compared with patients without neurocognitive and psychiatric disorders, patients with neurocognitive and psychiatric disorders exhibited more extensive (posterior predominant) decreases in axonal density. Using LICA, ICVF demonstrated the highest contribution (59% weight) to the main effects of diagnosis that reflected widespread decreases in axonal density. These findings suggest that axonal loss is a major factor underlying WM pathology related to neurocognitive and psychiatric disorders in PD, whereas patients with neurocognitive and psychiatric disorders had broader axonal pathology, as compared with those without. LICA suggested that the ICVF can be used as a useful biomarker of microstructural changes in the WM related to neurocognitive and psychiatric disorders in PD.

To develop a rigid real-time prospective motion-corrected multiparametric mapping technique and to test the performance of quantitative estimates.

Nodding syndrome (NS) is a unique childhood-onset epileptic disorder that occurs predominantly in several regions of sub-Saharan Africa. The disease has been associated with Onchocerca volvulus (Ov)-induced immune responses and possible cross-reactivity with host proteins. The aim of this study was to compare structural changes in the brain on MRI between NS and other forms of onchocerciasis-associated epilepsies (OAEs) and to relate structural changes to the Ov-induced immune responses and level of disability.

This pilot study investigates structural alterations and their relationships with cognitive function in survivors of diffuse gliomas. Twenty-four survivors of diffuse gliomas (mean age 44.5 ± 11.5), from whom high-resolution T1-weighted images, neuropsychological tests, and self-report questionnaires were obtained, were analyzed. Patients were grouped by degree of cognitive impairment, and interregional correlations of cortical thickness were computed to generate morphometric correlation networks (MCNs). The results show that the cortical thickness of the right insula (R2 = 0.3025, p = 0.0054) was negatively associated with time since the last treatment, and the cortical thickness of the left superior temporal gyrus (R2 = 0.2839, p = 0.0107) was positively associated with cognitive performance. Multiple cortical regions in the default mode, salience, and language networks were identified as predominant nodes in the MCNs of survivors of diffuse gliomas. Compared to cognitively impaired patients, cognitively non-impaired patients tended to have higher network stability in network nodes removal analysis, especially when the fraction of removed nodes (among 66 nodes in total) exceeded 55%. These findings suggest that structural networks are altered in survivors of diffuse gliomas and that their cortical structures may also be adapting to support cognitive function during survivorship.

This study aimed to evaluate the accuracy and diagnostic test performance of the U-net-based segmentation method in neuromelanin magnetic resonance imaging (NM-MRI) compared to the established manual segmentation method for Parkinson's disease (PD) diagnosis.

The glymphatic system is a whole-brain perivascular network, which promotes CSF/interstitial fluid exchange. Alterations to this system may play a pivotal role in amyloid β (Aβ) accumulation. However, its involvement in Alzheimer's disease (AD) pathogenesis is not fully understood. Here, we investigated the changes in noninvasive MRI measurements related to the perivascular network in patients with mild cognitive impairment (MCI) and AD. Additionally, we explored the associations of MRI measures with neuropsychological score, PET standardized uptake value ratio (SUVR), and Aβ deposition.

Machine learning algorithms could be used as the basis for clinical decision-making aids to enhance clinical practice.

Degenerative cervical myelopathy (DCM) is a progressive condition characterized by degeneration of osseocartilaginous structures within the cervical spine resulting in compression of the spinal cord and presentation of clinical symptoms. Compared to healthy controls (HCs), studies have shown DCM patients experience structural and functional reorganization in the brain; however, sex-dependent cortical differences in DCM patients remains largely unexplored. In the present study, we investigate the role of sex differences on the structure of the cerebral cortex in DCM and determine how structural differences may relate to clinical measures of neurological function. T1-weighted structural MRI scans were acquired in 85 symptomatic and asymptomatic patients with DCM and 90 age-matched HCs. Modified Japanese Orthopedic Association (mJOA) scores were obtained for patients. A general linear model was used to determine vertex-level significant differences in gray matter volume (GMV) between the following groups (1) male HCs and female HCs, (2) male patients and female patients, (3) male patients and male HCs, and (4) female patients and female HCs. Within patients, males exhibited larger GMV in motor, language, and vision related brain regions compared to female DCM patients. Males demonstrated a significant positive correlation between GMV and mJOA score, in which patients with worsening neurological symptoms exhibited decreasing GMV primarily across somatosensory and motor related cortical regions. Females exhibited a similar association, albeit across a broader range of cortical areas including those involved in pain processing. In sensorimotor regions, female patients consistently showed smaller GMV compared with male patients, independent of mJOA score. Results from the current study suggest strong sex-related differences in cortical volume in patients with DCM, which may reflect hormonal influence or differing compensation mechanisms.

Globally, epilepsy is the most common chronic neurological disorder. The incidence in sub-Saharan Africa is 2-3 times higher than that in high income countries. Infection by Onchocerca volvulus may be an underlying risk factor for the high burden and based upon epidemiological associations, has been proposed to cause a group of disorders-Onchocerca associated epilepsies (OAE) like nodding syndrome (NS). To improve our understanding of the disease spectrum, we described the clinical, electroencephalographic (EEG) and magnetic resonance imaging (MRI) features of children with epilepsy and sero-positive for Onchocerca volvulus (possible OAEs other than nodding syndrome). Twenty-nine children and adolescents with non-nodding syndrome OAE in northern Uganda were enrolled. A diagnosis of OAE was made in patients with epilepsy and seizure onset after age 3 years, no reported exposure to perinatal severe febrile illness or traumatic brain injury, no syndromic epilepsy diagnosis and a positive Ov-16 ELISA test. Detailed clinical evaluation including psychiatric, diagnostic EEG, a diagnostic brain MRI (in 10 patients) and laboratory testing were performed. Twenty participants (69%) were male. The mean age was 15.9 (standard deviation [SD] 1.9) years while the mean age at seizure onset was 9.8 (SD 2.9) years. All reported normal early childhood development. The most common clinical presentation was a tonic-clonic seizure. The median number of seizures was 2 (IQR 1-4) in the previous month. No specific musculoskeletal changes, or cranial nerve palsies were reported, neither were any vision, hearing and speech difficulties observed. The interictal EEG was abnormal in the majority with slow wave background activity in 52% (15/29) while 41% (12/29) had focal epileptiform activity. The brain MRI showed mild to moderate cerebellar atrophy and varying degrees of atrophy of the frontal, parietal and occipital lobes. The clinical spectrum of epilepsies associated with Onchocerca may be broader than previously described. In addition, focal onset tonic-clonic seizures, cortical and cerebellar atrophy may be important brain imaging and clinical features.

As treatments for diffuse gliomas have advanced, survival for patients with gliomas has also increased. However, there remains limited knowledge on the relationships between brain connectivity and the lasting changes to cognitive function that glioma survivors often experience long after completing treatment. This resting-state functional magnetic resonance imaging (rs-fMRI) study explored functional connectivity (FC) alterations associated with cognitive function in survivors of gliomas. In this pilot study, 22 patients (mean age 43.8 ± 11.9) with diffuse gliomas who completed treatment within the past 10 years were evaluated using rs-fMRI and neuropsychological measures. Novel rs-fMRI analysis methods were used to account for missing brain in the resection cavity. FC relationships were assessed between cognitively impaired and non-impaired glioma patients, along with self-reported cognitive impairment, non-work daily functioning, and time with surgery. In the cognitively non-impaired patients, FC was stronger in the medial prefrontal cortex, rostral prefrontal cortex, and intraparietal sulcus compared to the impaired survivors. When examining non-work daily functioning, a positive correlation with FC was observed between the accumbens and the intracalcarine cortices, while a negative correlation with FC was observed between the parietal operculum cortex and the cerebellum. Additionally, worse self-reported cognitive impairment and worse non-work daily functioning were associated with increased FC between regions involved in cognition and sensorimotor processing. These preliminary findings suggest that neural correlates for cognitive and daily functioning in glioma patients can be revealed using rs-fMRI. Resting-state network alterations may serve as a biomarker for patients' cognition and functioning.

Using a fixel-based analysis (FBA), we assessed the fiber-specific white matter (WM) alterations in nonmedicated patients with early-stage Parkinson's disease (PD) with tremor-dominant (TD; n = 53; mean age, 61.7 ± 8.7 years) and postural instability and gait disorder (PIGD; n = 27; mean age, 57.8 ± 8.1 years) motor subtypes and age- and sex-matched healthy controls (HC; n = 43; mean age, 61.6 ± 9.2 years) from Parkinson's Progression Markers Initiative dataset. FBA revealed significantly increased macrostructural fiber cross section and a combination of fiber density and cross section metrics within the corticospinal tract in patients with TD-PD compared with HC. Nonetheless, no significant changes in FBA-derived metrics were found in patients with PIGD-PD compared with HC or patients with TD-PD. Our results may provide evidence of WM neural compensation mechanisms in patients with TD-PD marked by increases in fiber bundle size and the ability to relay information between brain regions.

Although the clinical efficacy of deep brain stimulation targeting the anterior nucleus (AN) and centromedian nucleus (CM) of the thalamus has been actively investigated for the treatment of medication-resistant epilepsy, few studies have investigated dynamic ictal changes in corticothalamic connectivity in human EEG recording. This study aims to establish the complex spatiotemporal dynamics of the ictal corticothalamic network associated with various seizure foci.

To characterize ictal EEG change in the centromedian (CM) and anterior nucleus (AN) of the thalamus, using stereoelectroencephalography (SEEG) recordings.