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Growing evidence suggests that a "prion-like" mechanism underlies the pathogenesis of many neurodegenerative disorders, including Parkinson's disease (PD). We extend and tailor previously developed quantitative and predictive network diffusion model (NDM) to PD, by specifically modeling the trans-neuronal spread of alpha-synuclein outward from the substantia nigra (SN). The model demonstrated the spatial and temporal patterns of PD from neuropathological and neuroimaging studies and was statistically validated using MRI deformation of 232 Parkinson's patients. After repeated seeding simulations, the SN was found to be the most likely seed region, supporting its unique lynchpin role in Parkinson's pathology spread. Other alternative spread models were also evaluated for comparison, specifically, random spread and distance-based spread; the latter tests for Braak's original caudorostral transmission theory. We showed that the distance-based spread model is not as well supported as the connectivity-based model. Intriguingly, the temporal sequencing of affected regions predicted by the model was in close agreement with Braak stages III-VI, providing what we consider a "computational Braak" staging system. Finally, we investigated whether the regional expression patterns of implicated genes contribute to regional atrophy. Despite robust evidence for genetic factors in PD pathogenesis, NDM outperformed regional genetic expression predictors, suggesting that network processes are far stronger mediators of regional vulnerability than innate or cell-autonomous factors. This is the first finding yet of the ramification of prion-like pathology propagation in Parkinson's, as gleaned from in vivo human imaging data. The NDM is potentially a promising robust and clinically useful tool for diagnosis, prognosis and staging of PD.

Animal data indicate that the recreational drug ecstasy (3,4-methylenedioxymethamphetamine) can damage brain serotonin neurons. However, human neuroimaging measurements of serotonin transporter binding, a serotonin neuron marker, remain contradictory, especially regarding brain areas affected; and the possibility that structural brain differences might account for serotonin transporter binding changes has not been explored. We measured brain serotonin transporter binding using [(11)C] N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine in 50 control subjects and in 49 chronic (mean 4 years) ecstasy users (typically one to two tablets bi-monthly) withdrawn from the drug (mean 45 days). A magnetic resonance image for positron emission tomography image co-registration and structural analyses was acquired. Hair toxicology confirmed group allocation but also indicated use of other psychoactive drugs in most users. Serotonin transporter binding in ecstasy users was significantly decreased throughout all cerebral cortices (range -19 to -46%) and hippocampus (-21%) and related to the extent of drug use (years, maximum dose), but was normal in basal ganglia and midbrain. Substantial overlap was observed between control and user values except for insular cortex, in which 51% of ecstasy user values fell below the lower limit of the control range. Voxel-based analyses confirmed a caudorostral gradient of cortical serotonin transporter binding loss with occipital cortex most severely affected. Magnetic resonance image measurement revealed no overall regional volume differences between groups; however, a slight left-hemispheric biased cortical thinning was detected in methamphetamine-using ecstasy users. The serotonin transporter binding loss was not related to structural changes or partial volume effect, use of other stimulant drugs, blood testosterone or oestradiol levels, major serotonin transporter gene promoter polymorphisms, gender, psychiatric status, or self-reported hyperthermia or tolerance. The ecstasy group, although 'grossly behaviourally normal', reported subnormal mood and demonstrated generally modest deficits on some tests of attention, executive function and memory, with the latter associated with serotonin transporter decrease. Our findings suggest that the 'typical'/low dose (one to two tablets/session) chronic ecstasy-polydrug user might display a highly selective mild to marked loss of serotonin transporter in cerebral cortex/hippocampus in the range of that observed in Parkinson's disease, which is not gender-specific or completely accounted for by structural brain changes, recent use of other drugs (as assessed by hair analyses) or other potential confounds that we could address. The striking sparing of serotonin transporter-rich striatum (although possibly affected in 'heavier' users) suggests that serotonergic neurons innervating cerebral cortex are more susceptible, for unknown reasons, to ecstasy than those innervating subcortical regions and that behavioural problems in some ecstasy users during abstinence might be related to serotonin transporter changes limited to cortical regions. [ABSTRACT FROM AUTHOR]

We propose that academic scholarship and clinical practice should conceptualize communication about risk as a dialogic and relational process. This conceptual paper addresses how clinical decisions about cancer treatment are impacted by different risk perceptions. Patients and health care providers base their risk perceptions on analytic or experiential reasoning processes. However, most risk communication research in the clinical context only examines the transmissive and persuasive communication of these different risk perceptions. This transmissive communication results in a monologic model that limits the opportunities for patients and clinicians to incorporate their perspectives into a shared understanding. The dialogic model of risk communication contributes to a quality cancer care decision because it creates open space to find connections between patient values and clinical evidence while allowing the parties to have a satisfactory level of involvement. The final section of the paper describes theory behind a dialogic perspective and offers guidelines for how to implement it in risk communication to improve clinical decision making. [ABSTRACT FROM AUTHOR]

BACKGROUND/AIMS: Differences in the gross shape of the corpus callosum (CC) and its subregional areas were investigated on brain MRI of patients with probable Alzheimer's disease (AD) and age- and gender-matched healthy normal control subjects. The AD patients differed from the normal control subjects in terms of a more convex shape and a reduced area of the CC. METHODS: As for the comparisons of the subregional areas of the CC, we adapted a splitting method which takes into account the modification of the global shape of the CC, and we implemented it by normalizing the CC, to avoid the bias introduced by the observed callosal shape variability. RESULTS: The application of this method unveiled that the regional CC reductions were located in the anterior and posterior third of the CC, i.e. where small myelinated fibers are more frequent. None of the neuropsychological scores collected at the time of the MRI investigation of AD could predict a regional and/or overall callosal area reduction. The only measure that correlated with area of the isthmus of the CC was the MMSE that was administered to all participants. CONCLUSIONS: This latter result may be used as an in vivo indicator of the progress of neocortical disintegration in AD. [ABSTRACT FROM AUTHOR]

Objective: To assess the reactions of parents and their children to the request for a blood sample and an attempt to take blood.Methods: 1859 children aged 1.5-4.5 years took part in a national survey of diet and nutrition. A retrospective inquiry of the parents' and children's reported reactions was carried out six to 18 months later by postal questionnaire sent only to the 1157 who had given consent for an attempt to take blood.Results: 866 questionnaires were returned; 790 were from parents of children in whom an attempt to take blood had been successful. Thirteen per cent said that their child had given blood previously. About 30% discussed the request with the family doctor or nurse. Some 90% said that they were given enough information and that the phlebotomist was sympathetic. Attempting to take blood caused upset in over 50%, which, in most, lasted for less than five minutes. A substantial minority were upset for up to 30 minutes and a few much longer. Bruising or bleeding occurred in 20-27%. Degree and duration of upset were both adversely associated with a failed attempt to obtain blood.Conclusion: The majority of preschool children experienced no more than a little upset of short duration after an attempt to take blood, but a substantial minority exhibited a greater degree of upset. These responses should be taken into account when assessing the benefits and risks of the procedure. The best equipment and expertise should be employed for taking blood as successful attempts are less upsetting. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate patient response to multiple impulse therapy provided by the PulStarFRAS (Sense Technology, Inc, Murrysville, Pa) for a variety of musculoskeletal symptoms encountered in clinical practice. METHODS: A retrospective analysis of patient files was used to determine symptomatic improvement over the course of treatment. The multiple impulse therapy was supplemented, at the discretion of the practitioner, with manual adjustments. The manual adjustments consisted of high-velocity low-amplitude and drop table, and represented fewer than 5% of the adjustments. Therapy was provided by a single practitioner in a private clinic setting. RESULTS: Patients expressed improvement in symptoms after the first visit (average improvement in subjective pain rating scale of 41%). Patient symptoms improved between the first and second visits for 70% of patients (average improvement in subjective pain scale for all patients was 58%). The majority of patients achieved complete resolution of symptoms between the third and fourth visits. Maximum benefit for patients across all symptoms required an average of 4.2 visits. The half-life for response to multiple impulse therapy for all symptoms was 17 to 26 days. The half-life for response to multiple impulse therapy using the PulStarFRAS for low back pain was 9 to 16 days. CONCLUSION: The results of this study suggest the further study of multiple impulse therapy provided by the PulStarFRAS as a means of resolving musculoskeletal complaints. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is marked by the death of neuromelanin-rich dopaminergic and noradrenergic cells in the substantia nigra (SN) and the locus coeruleus (LC), respectively, resulting in motor and cognitive impairments. While SN dopamine dysfunction has clear neurophysiological effects, the association of reduced LC norepinephrine signaling with brain activity in PD remains to be established. We used neuromelanin-sensitive T1-weighted MRI (NPD = 58; NHC = 27) and task-free magnetoencephalography (NPD = 58; NHC = 65) to identify neuropathophysiological factors related to the degeneration of the LC and SN in patients with PD. We found pathological increases in rhythmic alpha (8-12 Hz) activity in patients with decreased LC neuromelanin, with a stronger association in patients with worse attentional impairments. This negative alpha-LC neuromelanin relationship is strongest in fronto-motor cortices, where alpha activity is inversely related to attention scores. Using neurochemical colocalization analyses with normative atlases of neurotransmitter transporters, we also show that this effect is more pronounced in regions with high densities of norepinephrine transporters. These observations support a noradrenergic association between LC integrity and alpha band activity. Our data also show that rhythmic beta (15-29 Hz) activity in the left somato-motor cortex decreases with lower levels of SN neuromelanin; the same regions where beta activity reflects axial motor symptoms. Together, our findings clarify the association of well-documented alterations of rhythmic neurophysiology in PD with cortical and subcortical neurochemical systems. Specifically, attention-related alpha activity is related to dysfunction of the noradrenergic system, and beta activity with relevance to motor impairments reflects dopaminergic dysfunction., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Nucleus Basalis of Meynert (NbM), a crucial source of cholinergic projection to the entorhinal cortex (EC) and hippocampus (HC), has shown sensitivity to neurofibrillary degeneration in the early stages of Alzheimer's Disease. Using deformation-based morphometry (DBM) on up-sampled MRI scans from 1447 Alzheimer's Disease Neuroimaging Initiative participants, we aimed to quantify NbM degeneration along the disease trajectory. Results from cross-sectional analysis revealed significant differences of NbM volume between cognitively normal and early mild cognitive impairment cohorts, confirming recent studies suggesting that NbM degeneration happens before degeneration in the EC or HC. Longitudinal linear mixed-effect models were then used to compare trajectories of volume change after realigning all participants into a common timeline based on their cognitive decline. Results indicated the earliest deviations in NbM volumes from the cognitively healthy trajectory, challenging the prevailing idea that Alzheimer's originates in the EC. Converging evidence from cross-sectional and longitudinal models suggest that the NbM may be a focal target of early AD progression, which is often obscured by normal age-related decline., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent studies have shown that white-gray contrast (WGC) of either cortical or subcortical gray matter provides for accurate predictions of age in typically developing (TD) children, and that, at least for the cortex, it changes differently with age in subjects with autism spectrum disorder (ASD) compared to their TD peers. Our previous study showed different patterns of contrast change between ASD and TD in sensorimotor and association cortices. While that study was confined to the cortex, we hypothesized that subcortical structures, particularly the thalamus, were involved in the observed cortical dichotomy between lower and higher processing. The current paper investigates that hypothesis using the WGC measures from the thalamus in addition to those from the cortex. We compared age-related WGC changes in the thalamus to those in the cortex. To capture the simultaneity of this change across the two structures, we devised a metric capturing the co-development of the thalamus and cortex (CoDevTC), proportional to the magnitude of cortical and thalamic age-related WGC change. We calculated this metric for each of the subjects in a large homogeneous sample taken from the Autism Brain Imaging Data Exchange (ABIDE) (N = 434). We used structural MRI data from the largest high-quality cross-sectional sample (NYU) as well as two other large high-quality sites, GU and OHSU, all three using Siemens 3T scanners. We observed that the co-development features in ASD and TD exhibit contrasting patterns; specifically, some higher-order thalamic nuclei, such as the lateral dorsal nucleus, exhibited reduction in codevelopment with most of the cortex in ASD compared to TD. Moreover, this difference in the CoDevTC pattern correlates with a number of behavioral measures across multiple cognitive and physiological domains. The results support previous notions of altered connectivity in autism, but add more specific evidence about the heterogeneity in thalamocortical development that elucidates the mechanisms underlying the clinical features of ASD., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The volume of the lateral ventricles is a reliable and sensitive indicator of brain atrophy and disease progression in behavioural variant frontotemporal dementia. In this study, we validate our previously developed automated tool using ventricular features (known as VentRa) for the classification of behavioural variant frontotemporal dementia versus a mixed cohort of neurodegenerative, vascular and psychiatric disorders from a clinically representative independent dataset. Lateral ventricles were segmented for 1110 subjects-14 behavioural variant frontotemporal dementia, 30 other frontotemporal dementia, 70 Lewy body disease, 898 Alzheimer's disease, 62 vascular brain injury and 36 primary psychiatric disorder from the publicly accessible National Alzheimer's Coordinating Center dataset to assess the performance of VentRa. Using ventricular features to discriminate behavioural variant frontotemporal dementia subjects from primary psychiatric disorders, VentRa achieved an accuracy rate of 84%, a sensitivity rate of 71% and a specificity rate of 89%. VentRa was able to identify behavioural variant frontotemporal dementia from a mixed age-matched cohort (i.e. other frontotemporal dementia, Lewy body disease, Alzheimer's disease, vascular brain injury and primary psychiatric disorders) and to correctly classify other disorders as 'not compatible with behavioral variant frontotemporal dementia' with a specificity rate of 83%. The specificity rates against each of the other individual cohorts were 80% for other frontotemporal dementia, 83% for Lewy body disease, 83% for Alzheimer's disease, 84% for vascular brain injury and 89% for primary psychiatric disorders. VentRa is a robust and generalizable tool with potential usefulness for improving the diagnostic certainty of behavioural variant frontotemporal dementia, particularly for the differential diagnosis with primary psychiatric disorders., Competing Interests: D.L.C. is the co-founder of True Positive Medical Devices. S.D. is the co-founder of AFX Medical Inc. The other authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The apolipoprotein (APOE) ɛ4 allele is a risk factor for Alzheimer's disease (AD), whereas the ɛ2 allele is thought to be protective against AD. Few studies have examined the relationship between brain pathologies, atrophy, white matter hyperintensities (WMHs) and APOE status in those with the ɛ2ɛ4 genotype and results are inconsistent for those with an ɛ2 allele. Alzheimer's disease neuroimaging participants were divided into 1 of 4 APOE allele profiles (E4 = ɛ4ɛ4 or ɛ3ɛ4; E2 = ɛ2ɛ2 or ɛ2ɛ3; E3 = ɛ3ɛ3; or E24 = ɛ2ɛ4). Linear mixed models examined the relationship between APOE profiles and brain changes (i.e., regional WMHs, ventricle size, hippocampal and entorhinal cortex volume, amyloid level, and phosphorylated tau measures), while controlling for age, sex, education, and diagnostic status at baseline and over time. APOE ɛ4 was associated with increased pathology, whereas ɛ2 positivity is associated with reduced baseline and lower accumulation of pathologies and neurodegeneration. APOE ɛ2ɛ4 was similar to ɛ4 (increased neurodegeneration) but with a slower rate of change. The strong associations observed between APOE and pathology show the importance of how genetic factors influence structural brain changes. These findings suggest that ɛ2ɛ4 genotype is related to increased declines associated with the ɛ4 as opposed to the protective effects of the ɛ2. These findings have important implications for initiating treatments and interventions. Given that people with the ɛ2ɛ4 genotype can expect to have increased atrophy, they should be considered (alongside those with an ɛ4) in targeted interventions to reduce brain changes that occur with AD., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives: Subpial corticectomy involving complete lesion resection while preserving pial membranes and avoiding injury to adjacent normal tissues is an essential bimanual task necessary for neurosurgical trainees to master. We sought to develop an ex vivo calf brain corticectomy simulation model with continuous assessment of surgical instrument movement during the simulation. A case series study of skilled participants was performed to assess face and content validity to gain insights into the utility of this training platform, along with determining if skilled and less skilled participants had statistical differences in validity assessment., Methods: An ex vivo calf brain simulation model was developed in which trainees performed a subpial corticectomy of three defined areas. A case series study assessed face and content validity of the model using 7-point Likert scale questionnaires., Results: Twelve skilled and 11 less skilled participants were included in this investigation. Overall median scores of 6.0 (range 4.0-6.0) for face validity and 6.0 (range 3.5-7.0) for content validity were determined on the 7-point Likert scale, with no statistical differences between skilled and less skilled groups identified., Conclusion: A novel ex vivo calf brain simulator was developed to replicate the subpial resection procedure and demonstrated face and content validity., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: White matter hyperintensities (WMHs) are associated with cognitive decline and progression to mild cognitive impairment (MCI) and dementia. It remains unclear if sex differences influence WMH progression or the relationship between WMH and cognition., Methods: Linear mixed models examined the relationship between risk factors, WMHs, and cognition in males and females., Results: Males exhibited increased WMH progression in occipital, but lower progression in frontal, total, and deep than females. For males, history of hypertension was the strongest contributor, while in females, the vascular composite was the strongest contributor to WMH burden. WMH burden was more strongly associated with decreases in global cognition, executive functioning, memory, and functional activities in females than males., Discussion: Controlling vascular risk factors may reduce WMH in both males and females. For males, targeting hypertension may be most important to reduce WMHs. The results have implications for therapies/interventions targeting cerebrovascular pathology and subsequent cognitive decline., Highlights: Hypertension is the main vascular risk factor associated with WMH in males A combination of vascular risk factors contributes to WMH burden in females Only small WMH burden differences were observed between sexes Females' cognition was more negatively impacted by WMH burden than males Females with WMHs may have less resilience to future pathology., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Blood-flow artifacts present a serious challenge for most, if not all, volumetric analytical approaches. We utilize T1-weighted data with prominent blood-flow artifacts from the Autism Brain Imaging Data Exchange (ABIDE) multisite agglomerative dataset to assess the impact that such blood-flow artifacts have on registration of T1-weighted data to a template. We use a heuristic approach to identify the blood-flow artifacts in these data; we use the resulting blood masks to turn the underlying voxels to the intensity of the cerebro-spinal fluid, thus mimicking the effect of blood suppression. We then register both the original data and the deblooded data to a common T1-weighted template, and compare the quality of those registrations to the template in terms of similarity to the template. The registrations to the template based on the deblooded data yield significantly higher similarity values compared with those based on the original data. Additionally, we measure the nonlinear deformations needed to transform the data from the position achieved by registering the original data to the template to the position achieved by registering the deblooded data to the template. The results indicate that blood-flow artifacts may seriously impact data processing that depends on registration to a template, that is, most all data processing., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Deep learning algorithms have greatly improved our ability to estimate eloquent cortex regions from resting-state brain scans for patients about to undergo neurosurgery. The use of deep learning has the potential to fully automate functional mapping of cortex in this context. We present a highly focused state-of-the-art review on current technology for estimating eloquent cortex from resting-state functional magnetic resonance scans and identify potential paths to meet this goal in the future., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Image-guided neurosurgery allows surgeons to view their tools in relation to preoperatively acquired patient images and models. To continue using neuronavigation systems throughout operations, image registration between preoperative images [typically magnetic resonance imaging (MRI)] and intraoperative images (e.g., ultrasound) is common to account for brain shift (deformations of the brain during surgery). We implemented a method to estimate MRI-ultrasound registration errors, with the goal of enabling surgeons to quantitatively assess the performance of linear or nonlinear registrations. To the best of our knowledge, this is the first dense error estimating algorithm applied to multimodal image registrations. The algorithm is based on a previously proposed sliding-window convolutional neural network that operates on a voxelwise basis. To create training data where the true registration error is known, simulated ultrasound images were created from preoperative MRI images and artificially deformed. The model was evaluated on artificially deformed simulated ultrasound data and real ultrasound data with manually annotated landmark points. The model achieved a mean absolute error (MAE) of 0.977 ± 0.988 mm and a correlation of 0.8 ± 0.062 on the simulated ultrasound data, and an MAE of 2.24 ± 1.89 mm and a correlation of 0.246 on the real ultrasound data. We discuss concrete areas to improve the results on real ultrasound data. Our progress lays the foundation for future developments and ultimately implementation of clinical neuronavigation systems.

Much research has focused on neurodegeneration in aging and Alzheimer's disease (AD). We developed Scoring by Nonlocal Image Patch Estimator (SNIPE), a non-local patch-based measure of anatomical similarity and hippocampal segmentation to measure hippocampal change. While SNIPE shows enhanced predictive power over hippocampal volume, it is unknown whether SNIPE is more strongly associated with group differences between normal controls (NC), early MCI (eMCI), late (lMCI), and AD than hippocampal volume. Alzheimer's Disease Neuroimaging Initiative older adults were included in the first analyses (N = 1666, 513 NCs, 269 eMCI, 556 lMCI, and 328 AD). Sub-analyses investigated amyloid positive individuals (N = 834; 179 NC, 148 eMCI, 298 lMCI, and 209 AD) to determine accuracy in those on the AD trajectory. We compared SNIPE grading, SNIPE volume, and Freesurfer volume as features in seven different machine learning techniques classifying participants into their correct cohort using 10-fold cross-validation. The best model was then validated in the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL). SNIPE grading provided the highest classification accuracy for all classifications in both the full and amyloid positive sample. When classifying NC:AD, SNIPE grading provided an 89% accuracy (full sample) and 87% (amyloid positive sample). Freesurfer volume provided much lower accuracies of 65% (full sample) and 46% (amyloid positive sample). In the AIBL validation cohort, SNIPE grading provided a 90% classification accuracy for NC:AD. These findings suggest SNIPE grading provides increased classification accuracy over both SNIPE and Freesurfer volume. SNIPE grading offers promise to accurately identify people with and without AD., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background and Objectives: Pediatric-acquired demyelination of the CNS associated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG; MOG antibody-associated disease [MOGAD]) occurs as a monophasic or relapsing disease and with variable but often extensive T2 lesions in the brain. The impact of MOGAD on brain growth during maturation is unknown. We quantified the effect of pediatric MOGAD on brain growth trajectories and compared this with the growth trajectories of age-matched and sex-matched healthy children and children with multiple sclerosis (MS, a chronic relapsing disease known to lead to failure of normal brain growth and to loss of brain volume) and monophasic seronegative demyelination., Methods: We included children enrolled at incident attack in the prospective longitudinal Canadian Pediatric Demyelinating Disease Study who were recruited at the 3 largest enrollment sites, underwent research brain MRI scans, and were tested for serum MOG-IgG. Children seropositive for MOG-IgG were diagnosed with MOGAD. MS was diagnosed per the 2017 McDonald criteria. Monophasic seronegative demyelination was confirmed in children with no clinical or MRI evidence of recurrent demyelination and negative results for MOG-IgG and aquaporin-4-IgG. Whole and regional brain volumes were computed through symmetric nonlinear registration to templates. We computed age-normalized and sex-normalized z scores for brain volume using a normative dataset of 813 brain MRI scans obtained from typically developing children and used mixed-effect models to assess potential deviation from brain growth trajectories., Results: We assessed brain volumes of 46 children with MOGAD, 26 with MS, and 51 with monophasic seronegative demyelinating syndrome. Children with MOGAD exhibited delayed ( p < 0.001) age-expected and sex-expected growth of thalamus, caudate, and globus pallidus, normalized for the whole brain volume. Divergence from expected growth was particularly pronounced in the first year postonset and was detected even in children with monophasic MOGAD. Thalamic volume abnormalities were less pronounced in children with MOGAD compared with those in children with MS., Discussion: The onset of MOGAD during childhood adversely affects the expected trajectory of growth of deep gray matter structures, with accelerated changes in the months after an acute attack. Further studies are required to better determine the relative impact of monophasic vs relapsing MOGAD and whether relapsing MOGAD with attacks isolated to the optic nerves or spinal cord affects brain volume over time., (© 2023 American Academy of Neurology.)

Early detection of Alzheimer's disease is essential to develop preventive treatment strategies. Detectible change in brain volume emerges relatively late in the pathogenic progression of disease, but microstructural changes caused by early neuropathology may cause subtle changes in the MR signal, quantifiable using texture analysis. Texture analysis quantifies spatial patterns in an image, such as smoothness, randomness and heterogeneity. We investigated whether the MRI texture of the hippocampus, an early site of Alzheimer's disease pathology, is sensitive to changes in brain microstructure before the onset of cognitive impairment. We also explored the longitudinal trajectories of hippocampal texture across the Alzheimer's continuum in relation to hippocampal volume and other biomarkers. Finally, we assessed the ability of texture to predict future cognitive decline, over and above hippocampal volume. Data were acquired from the Alzheimer's Disease Neuroimaging Initiative. Texture was calculated for bilateral hippocampi on 3T T 1 -weighted MRI scans. Two hundred and ninety-three texture features were reduced to five principal components that described 88% of total variance within cognitively unimpaired participants. We assessed cross-sectional differences in these texture components and hippocampal volume between four diagnostic groups: cognitively unimpaired amyloid-β - ( n = 406); cognitively unimpaired amyloid-β + ( n = 213); mild cognitive impairment amyloid-β + ( n = 347); and Alzheimer's disease dementia amyloid-β + ( n = 202). To assess longitudinal texture change across the Alzheimer's continuum, we used a multivariate mixed-effects spline model to calculate a 'disease time' for all timepoints based on amyloid PET and cognitive scores. This was used as a scale on which to compare the trajectories of biomarkers, including volume and texture of the hippocampus. The trajectories were modelled in a subset of the data: cognitively unimpaired amyloid-β - ( n = 345); cognitively unimpaired amyloid-β + ( n = 173); mild cognitive impairment amyloid-β + ( n = 301); and Alzheimer's disease dementia amyloid-β + ( n = 161). We identified a difference in texture component 4 at the earliest stage of Alzheimer's disease, between cognitively unimpaired amyloid-β - and cognitively unimpaired amyloid-β + older adults (Cohen's d = 0.23, P adj = 0.014). Differences in additional texture components and hippocampal volume emerged later in the disease continuum alongside the onset of cognitive impairment ( d = 0.30-1.22, P adj < 0.002). Longitudinal modelling of the texture trajectories revealed that, while most elements of texture developed over the course of the disease, noise reduced sensitivity for tracking individual textural change over time. Critically, however, texture provided additional information than was provided by volume alone to more accurately predict future cognitive change ( d = 0.32-0.63, P adj < 0.0001). Our results support the use of texture as a measure of brain health, sensitive to Alzheimer's disease pathology, at a time when therapeutic intervention may be most effective., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Hippocampal changes are associated with increased age and cognitive decline due to mild cognitive impairment (MCI) and Alzheimer's disease (AD). These associations are often observed only in the later stages of decline. This study examined if hippocampal grading, a method measuring local morphological similarity of the hippocampus to cognitively normal controls (NCs) and AD participants, is associated with cognition in NCs, subjective cognitive decline (SCD), early (eMCI), late (lMCI), and AD. A total of 1620 Alzheimer's Disease Neuroimaging Initiative participants were examined (495 NC, 262 eMCI, 545 lMCI, and 318 AD) because they had baseline MRIs and Alzheimer's disease Assessment Scale (ADAS-13) and Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. In a sub-analysis, NCs with episodic memory scores (as measured by Rey Auditory Verbal Learning Test, RAVLT) were divided into those with subjective cognitive decline (SCD+; 103) and those without (SCD-; 390). Linear regressions evaluated the influence of hippocampal grading on cognition in preclinical and prodromal AD. Lower global cognition, as measured by increased ADAS-13, was associated with hippocampal grading: NC (p < .001), eMCI (p < .05), lMCI (p < .05), and AD (p = .01). Lower global cognition as measured increased CDR-SB was associated with hippocampal grading in lMCI (p < .05) and AD (p < .001). Lower RAVLT performance was associated with hippocampal grading in SCD- (p < .05) and SCD+ (p < .05). These findings suggest that hippocampal grading is associated with global cognition in NC, eMCI, lMCI, and AD. Early changes in episodic memory during pre-clinical AD are associated with changes in hippocampal grading. Hippocampal grading may be sensitive to progressive changes early in the disease course., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Objective. Accurate localization, classification, and visualization of intracranial electrodes are fundamental for analyzing intracranial electrographic recordings. While manual contact localization is the most common approach, it is time-consuming, prone to errors, and is particularly challenging and subjective in low quality images, which are common in clinical practice. Automatically locating and interactively visualizing where each of the 100-200 individual contacts records in the brain is essential for understanding the neural origins of intracranial EEG. Approach. We introduced the SEEGAtlas plugin for the IBIS system, an open-source software platform for image-guided neurosurgery and multi-modal image visualization. SEEGAtlas extends IBIS functionalities to semi-automatically locate depth-electrode contact coordinates and automatically label the tissue type and anatomical region in which each contact is located. To illustrate the capabilities of SEEGAtlas and to validate the algorithms, clinical magnetic resonance images (MRIs) before and after electrode implantation of ten patients with depth electrodes implanted to localize the origin of their epileptic seizures were analyzed. Main Results . Visually identified contact coordinates were compared with the coordinates obtained by SEEGAtlas, resulting in a median difference of 1.4 mm. The agreement was lower for MRIs with weak susceptibility artifacts than for high-quality images. The tissue type was classified with 86% agreement with visual inspection. The anatomical region was classified as having a median agreement across patients of 82%. Significance . The SEEGAtlas plugin is user-friendly and enables accurate localization and anatomical labeling of individual contacts along implanted electrodes, together with powerful visualization tools. Employing the open-source SEEGAtlas results in accurate analysis of the recorded intracranial electroencephalography (EEG), even when only suboptimal clinical imaging is available. A better understanding of the cortical origin of intracranial EEG would help improve clinical interpretation and answer fundamental questions of human neuroscience., (© 2023 IOP Publishing Ltd.)

Exposures to prenatal maternal depressive symptoms (PMDS) may lead to neurodevelopmental changes in the offspring in a sex-dependent way. Although a connection between PMDS and infant brain development has been established by earlier studies, the relationship between PMDS exposures measured at various prenatal stages and microstructural alterations in fundamental subcortical structures such as the amygdala remains unknown. In this study, we investigated the associations between PMDS measured during gestational weeks 14, 24 and 34 and infant amygdala microstructural properties using diffusion tensor imaging. We explored amygdala mean diffusivity (MD) alterations in response to PMDS in infants aged 11 to 54 days from birth. PMDS had no significant main effect on the amygdala MD metrics. However, there was a significant interaction effect for PMDS and infant sex in the left amygdala MD. Compared with girls, boys exposed to greater PMDS during gestational week 14 showed significantly higher left amygdala MD. These results indicate that PMDS are linked to infants' amygdala microstructure in boys. These associations may be relevant to later neuropsychiatric outcomes in the offspring. Further research is required to better understand the mechanisms underlying these associations and to develop effective interventions to counteract any potential adverse consequences., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Parkinson's disease (PD) is a complex neurodegenerative disorder affecting regions such as the substantia nigra (SN), red nucleus (RN) and locus coeruleus (LC). Processing MRI data from patients with PD requires anatomical structural references for spatial normalization and structural segmentation. Extending our previous work, we present multi-contrast unbiased MRI templates using nine 3T MRI modalities: T1w, T2*w, T1-T2* fusion, R2*, T2w, PDw, fluid-attenuated inversion recovery (FLAIR), susceptibility-weighted imaging, and neuromelanin-sensitive MRI (NM). One mm isotropic voxel size templates were created, along with 0.5 mm isotropic whole brain templates and 0.3 mm isotropic templates of the midbrain. All templates were created from 126 PD patients (44 female; ages=40-87), and 17 healthy controls (13 female; ages=39-84), except the NM template, which was created from 85 PD patients and 13 controls, respectively. The dataset is available on the NIST MNI Repository via the following link: http://nist.mni.mcgill.ca/multi-contrast-pd126-and-ctrl17-templates/. The data is also available on NITRC at the following link: https://www.nitrc.org/projects/pd126/., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Inc.)

Prenatal adversity has been linked to later psychopathology. Yet, research on cumulative prenatal adversity, as well as its interaction with offspring genotype, on brain and behavioral development is scarce. With this study, we aimed to address this gap. In Finnish mother-infant dyads, we investigated the association of a cumulative prenatal adversity sum score (PRE-AS) with (a) child emotional and behavioral problems assessed with the Strengths and Difficulties Questionnaire at 4 and 5 years ( N = 1568, 45.3% female), (b) infant amygdalar and hippocampal volumes (subsample N = 122), and (c) its moderation by a hippocampal-specific coexpression polygenic risk score based on the serotonin transporter (SLC6A4) gene. We found that higher PRE-AS was linked to greater child emotional and behavioral problems at both time points, with partly stronger associations in boys than in girls. Higher PRE-AS was associated with larger bilateral infant amygdalar volumes in girls compared to boys, while no associations were found for hippocampal volumes. Further, hyperactivity/inattention in 4-year-old girls was related to both genotype and PRE-AS, the latter partially mediated by right amygdalar volumes as preliminary evidence suggests. Our study is the first to demonstrate a dose-dependent sexually dimorphic relationship between cumulative prenatal adversity and infant amygdalar volumes.

White matter hyperintensities (WMHs) may be one of the earliest pathological changes in aging. Race differences in WMH burden has been conflicting. This study examined if race influences WMHs and whether these differences are influenced by vascular risk factors. Alzheimer's Disease Neuroimaging Initiative participants were included if they had a baseline MRI, diagnosis, and WMH measurements. Ninety-one Blacks and 1937 Whites were included. Using bootstrap re-sampling, 91 Whites were randomly sampled and matched to Blacks based on age, sex, education, and diagnosis 1000 times. Linear models examined the influence of race on baseline WMHs, and change of WMHs over time, with and without vascular factors. Vascular risk factors had higher prevalence in Blacks than Whites. When not including vascular factors, Blacks had greater frontal, parietal, deep, and total WMH burden compared to Whites. There were no race differences in longitudinal progression of WMH accumulation. After controlling for vascular factors, only overall longitudinal parietal WMH group differences remained significant, suggesting that vascular factors contribute to racial group differences observed in WMHs., Competing Interests: Disclosure statement The authors have no actual or potential conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Increased age and cognitive impairment is associated with an increase in cerebrovascular pathology often measured as white matter hyperintensities (WMHs) on MRI. Whether WMH burden differs between cognitively unimpaired older adults with subjective cognitive decline (SCD +) and without subjective cognitive decline (SCD -) remains conflicting, and could be related to the methods used to identify SCD. Our goal was to examine if four common SCD classification methods are associated with different WMH accumulation patterns between SCD + and SCD - . A total of 535 cognitively unimpaired older adults with 1353 time points from the Alzheimer's Disease Neuroimaging Initiative were included in this study. SCD was operationalized using four different methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog + Worry, and Worry. Linear mixed-effects models were used to investigate the associations between SCD and overall and regional WMH burden. Overall temporal WMH burden differences were only observed with the Worry questionnaire. Higher WMH burden change over time was observed in SCD + compared to SCD - in the temporal and parietal regions using the CCI (temporal, p = .01; parietal p = .02) and ECog (temporal, p = .02; parietal p = .01). For both the ECog + Worry and Worry questionnaire, change in WMH burden over time was increased in SCD + compared to SCD - for overall, frontal, temporal, and parietal WMH burden (p < .05). These results show that WMH burden differs between SCD + and SCD - depending on the questionnaire and the approach (regional/global) used to measure WMHs. The various methods used to define SCD may reflect different types of underlying pathologies., (© 2022. The Author(s), under exclusive licence to American Aging Association.)

Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioural variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural network organization remains unknown. Here we investigate whether neurodegeneration patterns in sporadic and genetic bvFTD are conditioned by connectome architecture. Regional atrophy patterns were estimated in both genetic bvFTD (75 patients, 247 controls) and sporadic bvFTD (70 patients, 123 controls). First, we identified distributed atrophy patterns in bvFTD, mainly targeting areas associated with the limbic intrinsic network and insular cytoarchitectonic class. Regional atrophy was significantly correlated with atrophy of structurally- and functionally-connected neighbours, demonstrating that network structure shapes atrophy patterns. The anterior insula was identified as the predominant group epicentre of brain atrophy using data-driven and simulation-based methods, with some secondary regions in frontal ventromedial and antero-medial temporal areas. We found that FTD-related genes, namely C9orf72 and TARDBP, confer local transcriptomic vulnerability to the disease, modulating the propagation of pathology through the connectome. Collectively, our results demonstrate that atrophy patterns in sporadic and genetic bvFTD are jointly shaped by global connectome architecture and local transcriptomic vulnerability, providing an explanation as to how heterogenous pathological entities can lead to the same clinical syndrome., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: Germline variants in CDH1 are associated with elevated risks of diffuse gastric cancer and lobular breast cancer. It is uncertain whether there is an increased risk of colorectal neoplasia., Methods: This was a retrospective analysis of colonoscopy outcomes in patients with germline CDH1 pathogenic/likely pathogenic variants., Results: Eighty-five patients were included with a mean age of 46.9 years. Initial colonoscopy found adenomatous polyps in 30 patients (35.3%), including advanced adenomas in 9 (10.6%). No colorectal cancers were identified on index or subsequent colonoscopies (when available)., Discussion: CDH1 carriers have colorectal neoplasia identified at similar rates as in the general population. Despite potential difficulties after gastrectomy, colorectal cancer screening remains important in this population., (Copyright © 2022 by The American College of Gastroenterology.)

The corpus callosum (CC) is the largest fiber tract in the human brain, allowing interhemispheric communication by connecting homologous areas of the two cerebral hemispheres. In adults, CC size shows a robust allometric relationship with brain size, with larger brains having larger callosa, but smaller brains having larger callosa relative to brain size. Such an allometric relationship has been shown in both males and females, with no significant difference between the sexes. But there is some evidence that there are alterations in these allometric relationships during development. However, it is currently not known whether there is sexual dimorphism in these allometric relationships from birth, or if it only develops later. We study this in neonate data. Our results indicate that there are already sex differences in these allometric relationships in neonates: male neonates show the adult-like allometric relationship between CC size and brain size; however female neonates show a significantly more positive allometry between CC size and brain size than either male neonates or female adults. The underlying cause of this sexual dimorphism is unclear; but the existence of this sexual dimorphism in neonates suggests that sex-differences in lateralization have prenatal origins., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

In this work, a hierarchical search algorithm is proposed to efficiently compute the distance between similar tractography streamlines. This hierarchical framework offers an upper bound and a lower bound for the point-wise distance between two streamlines, which guarantees the validity of a proximity search. The proposed streamline representation enables the use of space-partitioning search trees to increase the tractography clustering speed without reducing its accuracy. The resulting approach enables a fast reconstruction a sparse distance matrix between two sets of streamlines, for all similar streamlines within a given radius. Alongside a white matter atlas, this fast streamline search can be used for accurate and reproducible tractogram clustering., (© 2022. The Author(s).)

Given that image registration is a fundamental and ubiquitous task in both clinical and research domains of the medical field, errors in registration can have serious consequences. Since such errors can mislead clinicians during image-guided therapies or bias the results of a downstream analysis, methods to estimate registration error are becoming more popular. To give structure to this new heterogenous field we developed a taxonomy and performed a scoping review of methods that quantitatively and automatically provide a dense estimation of registration error. The taxonomy breaks down error estimation methods into Approach (Image- or Transformation-based), Framework (Machine Learning or Direct) and Measurement (error or confidence) components. Following the PRISMA guidelines for scoping reviews, the 570 records found were reduced to twenty studies that met inclusion criteria, which were then reviewed according to the proposed taxonomy. Trends in the field, advantages and disadvantages of the methods, and potential sources of bias are also discussed. We provide suggestions for best practices and identify areas of future research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)