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Data processing techniques in transient electromagnetic (TEM) methods face numerous challenges, such as the problem of 3-D imaging and the demand for new data processing techniques arising from the development of small-loop TEM devices. We have developed an imaging algorithm based on gradient features derived from TEM data to address these challenges. We found that normalising the gradient field of TEM responses under appropriate background conditions enables imaging of the target. Numerical experiments conducted under theoretical models have validated the feasibility of this approach and highlighted the significance of background fields. We further designed more complex models and achieved 3-D imaging of synthetic data within seconds, demonstrating the method's high efficiency and applicability to high-dimensional data. Subsequently, we applied the algorithm to challenging small-loop TEM data and demonstrated its superior performance compared to the inversion method, which presents a novel approach for processing data from small-loop TEM devices. This study demonstrates that the algorithm possesses characteristics of high efficiency and wide applicability, suitable for TEM data from various dimensions and types of devices. Furthermore, it holds promising potential in assisting the enhancement of the efficiency of the three-dimensional inversion of TEM data. [ABSTRACT FROM AUTHOR]

Background: Previous studies have established a connection between adverse childhood experiences (ACE) and alcohol use disorder (AUD), both of which are associated with alterations in grey matter volume (GMV) and cortical thickness (CT). The current study aimed to assess the neurobiological impact of ACE specifically in the context of AUD, as well as the role of maltreatment type (i.e., abuse or neglect) and timing. Methods: Structural MRI data were collected from 35 adults with AUD (mean age: 40; 31% female) and 28 healthy controls (mean age: 36; 61% female). ACE were assessed retrospectively using the Childhood Trauma Questionnaire, and the Maltreatment and Abuse Chronology interview. Global and regional GMV and CT were estimated using voxel‐ and surface‐based morphometry. Results: Relative to the healthy controls, the AUD group had significantly reduced CT in the left inferior frontal gyrus, left circular sulcus of the insula and subcentral gyrus and sulci (cluster C1), and in the central sulcus and precentral gyrus (cluster C2). Within the AUD group, a reduction of CT in cluster C1 was significantly associated with higher severity of ACE and AUD. Type and timing analyses revealed a significant association between higher levels of abuse at ages 13 to 15 and reduced CT in cluster C1 within the AUD group. Conclusions: In adults with AUD, abuse experienced during early adolescence is associated with reduced CT in regions involved in inhibitory control, indicating the potential relevance of cognitive pathways in the association between ACE and AUD. Longitudinal studies are needed to confirm and expand upon current findings. [ABSTRACT FROM AUTHOR]

Accurate segmentation of thalamic nuclei, crucial for understanding their role in healthy cognition and in pathologies, is challenging to achieve on standard T1-weighted (T1w) magnetic resonance imaging (MRI) due to poor image contrast. White-matter-nulled (WMn) MRI sequences improve intrathalamic contrast but are not part of clinical protocols or extant databases. In this study, we introduce histogram-based polynomial synthesis (HIPS), a fast preprocessing transform step that synthesizes WMn-like image contrast from standard T1w MRI using a polynomial approximation for intensity transformation. HIPS was incorporated into THalamus Optimized Multi-Atlas Segmentation (THOMAS) pipeline, a method developed and optimized for WMn MRI. HIPS-THOMAS was compared to a convolutional neural network (CNN)-based segmentation method and THOMAS modified for the use of T1w images (T1w-THOMAS). The robustness and accuracy of the three methods were tested across different image contrasts (MPRAGE, SPGR, and MP2RAGE), scanner manufacturers (PHILIPS, GE, and Siemens), and field strengths (3 T and 7 T). HIPS-transformed images improved intra-thalamic contrast and thalamic boundaries, and HIPS-THOMAS yielded significantly higher mean Dice coefficients and reduced volume errors compared to both the CNN method and T1w-THOMAS. Finally, all three methods were compared using the frequently travelling human phantom MRI dataset for inter- and intra-scanner variability, with HIPS displaying the least inter-scanner variability and performing comparably with T1w-THOMAS for intra-scanner variability. In conclusion, our findings highlight the efficacy and robustness of HIPS in enhancing thalamic nuclei segmentation from standard T1w MRI. [ABSTRACT FROM AUTHOR]

BACKGROUND: Traumatic brain injury (TBI) can alter brain structure and lead to onset of persistent neuropsychological symptoms. This study investigates the relationship between brain injury and psychological distress after mild TBI using multimodal magnetic resonance imaging. METHODS: A total of 89 patients with mild TBI from the TRACK-TBI (Transforming Research and Clinical Knowledge in Traumatic Brain Injury) pilot study were included. Subscales of the Brief Symptoms Inventory 18 for depression, anxiety, and somatization were used as outcome measures of psychological distress approximately 6 months after the traumatic event. Glasgow Coma Scale scores were used to evaluate recovery. Magnetic resonance imaging data were acquired within 2 weeks after injury. Perivascular spaces (PVSs) were segmented using an enhanced PVS segmentation method, and the volume fraction was calculated for the whole brain and white matter regions. Cortical thickness and gray matter structures volumes were calculated in FreeSurfer; diffusion imaging indices and multifiber tracts were extracted using the Quantitative Imaging Toolkit. The analysis was performed considering age, sex, intracranial volume, educational attainment, and improvement level upon discharge as covariates. RESULTS: PVS fractions in the posterior cingulate, fusiform, and postcentral areas were found to be associated with somatization symptoms. Depression, anxiety, and somatization symptoms were associated with the cortical thickness of the frontal-opercularis and occipital pole, putamen and amygdala volumes, and corticospinal tract and superior thalamic radiation. Analyses were also performed on the two hemispheres separately to explore lateralization. CONCLUSIONS: This study shows how PVS, cortical, and microstructural changes can predict the onset of depression, anxiety, and somatization symptoms in patients with mild TBI.

Introduction: Maximal grip strength, a measure of how much force a person's hand can generate when squeezing an object, may be an effective method for understanding potential neurobiological differences during motor tasks. Grip strength in autistic individuals may be of particular interest due to its unique developmental trajectory. While autism-specific differences in grip-brain relationships have been found in adult populations, it is possible that such differences in grip-brain relationships may be present at earlier ages when grip strength is behaviorally similar in autistic and non-autistic groups. Further, such neural differences may lead to the later emergence of diagnostic-group grip differences in adolescence. The present study sought to examine this possibility, while also examining if grip strength could elucidate the neuro-motor sources of phenotypic heterogeneity commonly observed within autism. Methods: Using high resolution, multi-shell diffusion, and quantitative R1 relaxometry imaging, this study examined how variations in key sensorimotorrelated white matter pathways of the proprioception input, lateral grasping, cortico-cerebellar, and corticospinal networks were associated with individual variations in grip strength in 68 autistic children and 70 non-autistic (neurotypical) children (6-11 years-old). Results: In both groups, results indicated that stronger grip strength was associated with higher proprioceptive input, lateral grasping, and corticospinal (but not cortico-cerebellar modification) fractional anisotropy and R1, indirect measures concordant with stronger microstructural coherence and increased myelination. Diagnostic group differences in these grip-brain relationships were not observed, but the autistic group exhibited more variability particularly in the cortico-cerebellar modification indices. An examination into the variability within the autistic group revealed that attention-deficit/hyperactivity disorder (ADHD) features moderated the relationships between grip strength and both fractional anisotropy and R1 relaxometry in the premotor-primary motor tract of the lateral grasping network and the cortico-cerebellar network tracts. Specifically, in autistic children with elevated ADHD features (60% of the autistic group) stronger grip strength was related to higher fractional anisotropy and R1 of the cerebellar modification network (stronger microstructural coherence and more myelin), whereas the opposite relationship was observed in autistic children with reduced ADHD features. Discussion: Together, this work suggests that while the foundational elements of grip strength are similar across school-aged autistic and non-autistic children, neural mechanisms of grip strength within autistic children may additionally depend on the presence of ADHD features. Specifically, stronger, more coherent connections of the cerebellar modification network, which is thought to play a role in refining and optimizing motor commands, may lead to stronger grip in children with more ADHD features, weaker grip in children with fewer ADHD features, and no difference in grip in non-autistic children. While future research is needed to understand if these findings extend to other motor tasks beyond grip strength, these results have implications for understanding the biological basis of neuromotor control in autistic children and emphasize the importance of assessing co-occurring conditions when evaluating brain-behavior relationships in autism. [ABSTRACT FROM AUTHOR]

Introduction: Normal Pressure Hydrocephalus (NPH) is a prominent type of reversible dementia that may be treated with shunt surgery, and it is crucial to differentiate it from irreversible degeneration caused by its symptomatic mimics like Alzheimer's Dementia (AD) and Parkinson's Disease (PD). Similarly, it is important to distinguish between (normal pressure) hydrocephalus and irreversible atrophy/degeneration which are among the chronic effects of Traumatic Brain Injury (cTBI), as the former may be reversed through shunt placement. The purpose of this review is to elucidate the structural imaging markers which may be foundational to the development of accurate, noninvasive, and accessible solutions to this problem. Methods: By searching the PubMed database for keywords related to NPH, AD, PD, and cTBI, we reviewed studies that examined the (1) distinct neuroanatomical markers of degeneration in NPH versus AD and PD, and atrophy versus hydrocephalus in cTBI and (2) computational methods for their (semi-) automatic assessment on Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans. Results: Structural markers of NPH and those that can distinguish it from AD have been well studied, but only a few studies have explored its structural distinction between PD. The structural implications of cTBI over time have been studied. But neuroanatomical markers that can predict shunt response in patients with either symptomatic idiopathic NPH or post-traumatic hydrocephalus have not been reliably established. MRI-based markers dominate this field of investigation as compared to CT, which is also reflected in the disproportionate number of MRI-based computational methods for their automatic assessment. Conclusion: Along with an up-to-date literature review on the structural neurodegeneration due to NPH versus AD/PD, and hydrocephalus versus atrophy in cTBI, this article sheds light on the potential of structural imaging markers as (differential) diagnostic aids for the timely recognition of patients with reversible (normal pressure) hydrocephalus, and opportunities to develop computational tools for their objective assessment. [ABSTRACT FROM AUTHOR]

Introduction: Crohn's disease (CD), one of the main phenotypes of inflammatory bowel disease (IBD), can affect any part of the gastrointestinal tract. It can impact the function of gastrointestinal secretions, as well as increasing the intestinal permeability leading to an aberrant immunological response and subsequent intestinal inflammation. Studies have reported anatomical and functional brain changes in Crohn's Disease patients (CDs), possibly due to increased inflammatory markers and microglial cells that play key roles in communicating between the brain, gut, and systemic immune system. To date, no studies have demonstrated similarities between morphological brain changes seen in IBD and brain morphometry observed in older healthy controls. Methods: For the present study, twelve young CDs in remission (M = 26.08 years, SD = 4.9 years, 7 male) were recruited from an IBD Clinic. Data from 12 young age-matched healthy controls (HCs) (24.5 years, SD = 3.6 years, 8 male) and 12 older HCs (59 years, SD = 8 years, 8 male), previously collected for a different study under a similar MR protocol, were analyzed as controls. T1 weighted images and structural image processing techniques were used to extract surface-based brain measures, to test our hypothesis that young CDs have different brain surface morphometry than their age-matched young HCs and furthermore, appear more similar to older HCs. The phonemic verbal fluency (VF) task (the Controlled Oral Word Association Test, COWAT) (Benton, 1976) was administered to test verbal cognitive ability and executive control. Results/Discussion: On the whole, CDs had more brain regions with differences in brain morphometry measures when compared to the young HCs as compared to the old HCs, suggesting that CD has an effect on the brain that makes it appear more similar to old HCs. Additionally, our study demonstrates this atypical brain morphometry is associated with function on a cognitive task. These results suggest that even younger CDs may be showing some evidence of structural brain changes that demonstrate increased resemblance to older HC brains rather than their similarly aged healthy counterparts. [ABSTRACT FROM AUTHOR]

IntroductionMaximal grip strength, a measure of how much force a person’s hand can generate when squeezing an object, may be an effective method for understanding potential neurobiological differences during motor tasks. Grip strength in autistic individuals may be of particular interest due to its unique developmental trajectory. While autism-specific differences in grip-brain relationships have been found in adult populations, it is possible that such differences in grip-brain relationships may be present at earlier ages when grip strength is behaviorally similar in autistic and non-autistic groups. Further, such neural differences may lead to the later emergence of diagnostic-group grip differences in adolescence. The present study sought to examine this possibility, while also examining if grip strength could elucidate the neuro-motor sources of phenotypic heterogeneity commonly observed within autism.MethodsUsing high resolution, multi-shell diffusion, and quantitative R1 relaxometry imaging, this study examined how variations in key sensorimotor-related white matter pathways of the proprioception input, lateral grasping, cortico-cerebellar, and corticospinal networks were associated with individual variations in grip strength in 68 autistic children and 70 non-autistic (neurotypical) children (6–11 years-old).ResultsIn both groups, results indicated that stronger grip strength was associated with higher proprioceptive input, lateral grasping, and corticospinal (but not cortico-cerebellar modification) fractional anisotropy and R1, indirect measures concordant with stronger microstructural coherence and increased myelination. Diagnostic group differences in these grip-brain relationships were not observed, but the autistic group exhibited more variability particularly in the cortico-cerebellar modification indices. An examination into the variability within the autistic group revealed that attention-deficit/hyperactivity disorder (ADHD) features moderated the relationships between grip strength and both fractional anisotropy and R1 relaxometry in the premotor-primary motor tract of the lateral grasping network and the cortico-cerebellar network tracts. Specifically, in autistic children with elevated ADHD features (60% of the autistic group) stronger grip strength was related to higher fractional anisotropy and R1 of the cerebellar modification network (stronger microstructural coherence and more myelin), whereas the opposite relationship was observed in autistic children with reduced ADHD features.DiscussionTogether, this work suggests that while the foundational elements of grip strength are similar across school-aged autistic and non-autistic children, neural mechanisms of grip strength within autistic children may additionally depend on the presence of ADHD features. Specifically, stronger, more coherent connections of the cerebellar modification network, which is thought to play a role in refining and optimizing motor commands, may lead to stronger grip in children with more ADHD features, weaker grip in children with fewer ADHD features, and no difference in grip in non-autistic children. While future research is needed to understand if these findings extend to other motor tasks beyond grip strength, these results have implications for understanding the biological basis of neuromotor control in autistic children and emphasize the importance of assessing co-occurring conditions when evaluating brain-behavior relationships in autism.

Frontal variant Alzheimer's disease (AD) manifests with either behavioral or dysexecutive syndromes. Recent efforts to gain a deeper understanding of this phenotype have led to a re-conceptualization of frontal AD. Behavioral (bAD) and dysexecutive (dAD) phenotypes could be considered subtypes, as suggested by both clinical and neuroimaging studies. In this review, we focused on imaging studies to highlight specific brain patterns in these two uncommon clinical AD phenotypes. Although studies did not compare directly these two variants, a common epicenter located in the frontal cortex could be inferred. On the contrary, 18F-FDG-PET findings suggested differing metabolic patterns, with bAD showing specific involvement of frontal regions and dAD exhibiting widespread alterations. Structural MRI findings confirmed this pattern, suggesting that degeneration might involve neural circuits associated with behavioral control in bAD and attentional networks in dAD. Furthermore, molecular imaging has identified different neocortical tau distribution in bAD and dAD patients compared to typical AD patients, although the distribution is remarkably heterogeneous. In contrast, Aβ deposition patterns are less differentiated between these atypical variants and typical AD. Although preliminary, these findings underscore the complexity of AD frontal phenotypes and suggest that they represent distinct entities. Further research is essential to refine our understanding of the pathophysiological mechanisms in frontal AD.

IntroductionNormal Pressure Hydrocephalus (NPH) is a prominent type of reversible dementia that may be treated with shunt surgery, and it is crucial to differentiate it from irreversible degeneration caused by its symptomatic mimics like Alzheimer’s Dementia (AD) and Parkinson’s Disease (PD). Similarly, it is important to distinguish between (normal pressure) hydrocephalus and irreversible atrophy/degeneration which are among the chronic effects of Traumatic Brain Injury (cTBI), as the former may be reversed through shunt placement. The purpose of this review is to elucidate the structural imaging markers which may be foundational to the development of accurate, noninvasive, and accessible solutions to this problem.MethodsBy searching the PubMed database for keywords related to NPH, AD, PD, and cTBI, we reviewed studies that examined the (1) distinct neuroanatomical markers of degeneration in NPH versus AD and PD, and atrophy versus hydrocephalus in cTBI and (2) computational methods for their (semi-) automatic assessment on Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans.ResultsStructural markers of NPH and those that can distinguish it from AD have been well studied, but only a few studies have explored its structural distinction between PD. The structural implications of cTBI over time have been studied. But neuroanatomical markers that can predict shunt response in patients with either symptomatic idiopathic NPH or post-traumatic hydrocephalus have not been reliably established. MRI-based markers dominate this field of investigation as compared to CT, which is also reflected in the disproportionate number of MRI-based computational methods for their automatic assessment.ConclusionAlong with an up-to-date literature review on the structural neurodegeneration due to NPH versus AD/PD, and hydrocephalus versus atrophy in cTBI, this article sheds light on the potential of structural imaging markers as (differential) diagnostic aids for the timely recognition of patients with reversible (normal pressure) hydrocephalus, and opportunities to develop computational tools for their objective assessment.

Left-right asymmetry of the human brain is one of its cardinal features, and also a complex, multivariate trait. Decades of research have suggested that brain asymmetry may be altered in psychiatric disorders. However, findings have been inconsistent and often based on small sample sizes. There are also open questions surrounding which structures are asymmetrical on average in the healthy population, and how variability in brain asymmetry relates to basic biological variables such as age and sex. Over the last 4 years, the ENIGMA-Laterality Working Group has published six studies of gray matter morphological asymmetry based on total sample sizes from roughly 3,500 to 17,000 individuals, which were between one and two orders of magnitude larger than those published in previous decades. A population-level mapping of average asymmetry was achieved, including an intriguing fronto-occipital gradient of cortical thickness asymmetry in healthy brains. ENIGMA's multi-dataset approach also supported an empirical illustration of reproducibility of hemispheric differences across datasets. Effect sizes were estimated for gray matter asymmetry based on large, international, samples in relation to age, sex, handedness, and brain volume, as well as for three psychiatric disorders: autism spectrum disorder was associated with subtly reduced asymmetry of cortical thickness at regions spread widely over the cortex; pediatric obsessive-compulsive disorder was associated with altered subcortical asymmetry; major depressive disorder was not significantly associated with changes of asymmetry. Ongoing studies are examining brain asymmetry in other disorders. Moreover, a groundwork has been laid for possibly identifying shared genetic contributions to brain asymmetry and disorders.

Viruses come in various shapes and sizes, and understanding their morphology is central to understanding their activity and function. The need for fast recognition and real-time fingerprinting methods for pathogenic viruses is a critical bottleneck in implementing many diagnostic and therapeutic techniques. In this work, nanopore tomography (NT) is implemented for fast measurements of the characteristic dimensions of viruses and the optimal operating conditions are explored. Using a small filamentous bacteriophage as a model, it is demonstrated that NT can detect geometrical features in a few-nanometer regime, with high throughput and accuracy, in aqueous conditions. The instrumental parameters are optimized to obtain virus diameter measurements that are robust to the uncertainties of the external parameters. Furthermore, NT is critically compared to various single-particle imaging techniques, with a particular emphasis on emerging helium ion microscopy (HIM). It is shown that, with proper operating procedures, HIM can reach a nanometer-scale resolution in viral metrology, while retaining a high throughput second only to NT. The high throughput of both techniques can foster sufficient statistics for a precise exploration of viral heterogeneity. [ABSTRACT FROM AUTHOR]

The menopausal transition has been proposed to put women at risk for undesirable neurological symptoms, including cognitive decline. Previous studies suggest that alterations in the hormonal milieu modulate brain structures associated with cognitive function. This structured review provides an overview of the relevant studies that have utilized MRI to report volumetric differences in the brain following menopause, and its correlations with the evaluated cognitive functions. We performed an electronic literature search using Medline (Ovid) and Scopus to identify studies that assessed the influence of menopause on brain structure with MRI. Fourteen studies met the inclusion criteria. Brain volumetric differences have been reported most frequently in the frontal and temporal cortices as well as the hippocampus. These regions are important for higher cognitive tasks and memory. Additionally, the deficit in verbal and visuospatial memory in postmenopausal women has been associated with smaller regional brain volumes. Nevertheless, the limited number of eligible studies and cross-sectional study designs warrant further research to draw more robust conclusions. [ABSTRACT FROM AUTHOR]

Background: Gray matter abnormalities are observed across the psychosis spectrum. The trajectory of these abnormalities in healthy adolescents reporting subthreshold psychotic experiences (PEs) may provide insight into the neural mechanisms underlying psychotic symptoms. The risk of psychosis and additional psychopathology is even higher among these individuals who also report childhood adversity/DSM-5 diagnoses. Thus, the aims of this longitudinal study were to investigate PE-related volumetric changes in young people, noting any effects of childhood adversity/DSM-5 diagnosis. Methods: A total of 211 young people 11 to 13 years of age participated in the initial Adolescent Brain Development study. PE classification was determined by expert consensus at each time point. Participants underwent neuroimaging at 3 time points over 6 years. A total of 76 participants with at least one scan were included in the final sample; 34 who met criteria for PEs at least once across all the time points (PE group) and 42 control subjects. Data from 20 bilateral regions of interest were extracted for linear mixed-effects analyses. Results: Right hippocampal volume increased over time in the control group, with no increase in the PE group (p = .00352). DSM-5 diagnosis and childhood adversity were not significantly associated with right hippocampal volume. There was no significant effect of group or interaction in any other region. Conclusions: These findings further implicate right hippocampal volumetric abnormalities in the pathophysiology underlying PEs. Furthermore, as suggested by previous studies in those at clinical high risk for psychosis and those with first-episode psychosis, it is possible that these deficits may be a marker for later clinical outcomes.

The menopausal transition has been proposed to put women at risk for undesirable neurological symptoms, including cognitive decline. Previous studies suggest that alterations in the hormonal milieu modulate brain structures associated with cognitive function. This structured review provides an overview of the relevant studies that have utilized MRI to report volumetric differences in the brain following menopause, and its correlations with the evaluated cognitive functions. We performed an electronic literature search using Medline (Ovid) and Scopus to identify studies that assessed the influence of menopause on brain structure with MRI. Fourteen studies met the inclusion criteria. Brain volumetric differences have been reported most frequently in the frontal and temporal cortices as well as the hippocampus. These regions are important for higher cognitive tasks and memory. Additionally, the deficit in verbal and visuospatial memory in postmenopausal women has been associated with smaller regional brain volumes. Nevertheless, the limited number of eligible studies and cross-sectional study designs warrant further research to draw more robust conclusions.

Objectives: (1) To delineate whether cognitive flexibility and inhibitory ability are neurocognitive markers of passive suicidal ideation (PSI), an early stage of suicide risk in depression and (2) to determine whether PSI is associated with volumetric differences in regions of the prefrontal cortex (PFC) in middle-aged and older adults with depression. Design: Cross-sectional study. Setting: University medical school. Participants: Forty community-dwelling middle-aged and older adults with depression from a larger study of depression and anxiety (NIMH R01 MH091342-05 PI: O'Hara). Measurements: Psychiatric measures were assessed for the presence of a DSM-5 depressive disorder and PSI. A neurocognitive battery assessed cognitive flexibility, inhibitory ability, as well as other neurocognitive domains. Results: The PSI group (n = 18) performed significantly worse on cognitive flexibility and inhibitory ability, but not on other neurocognitive tasks, compared to the group without PSI (n = 22). The group with PSI had larger left mid-frontal gyri (MFG) than the no-PSI group. There was no association between cognitive flexibility/inhibitory ability and left MFG volume. Conclusions: Findings implicate a neurocognitive signature of PSI: poorer cognitive flexibility and poor inhibitory ability not better accounted for by other domains of cognitive dysfunction and not associated with volumetric differences in the left MFG. This suggests that there are two specific but independent risk factors of PSI in middle- and older-aged adults. [ABSTRACT FROM AUTHOR]

Background: The connection between migraine aura and headache is poorly understood. Some patients experience migraine aura without headache, and patients with migraine aura with headache commonly experience milder headaches with age. The distance between the cerebral cortex and the overlying dura mater has been hypothesized to influence development of headache following aura. We tested this hypothesis by comparing approximated distances between visual cortical areas and overlying dura mater between female patients with migraine aura without headache and female patients with migraine aura with headache. Methods: Twelve cases with migraine aura without headache and 45 age-matched controls with migraine aura with headache underwent 3.0 T MRI. We calculated average distances between the occipital lobes, between the calcarine sulci, and between the skull and visual areas V1, V2 and V3a. We also measured volumes of corticospinal fluid between the occipital lobes, between the calcarine sulci, and overlying visual areas V2 and V3a. We investigated the relationship between headache status, distances and corticospinal fluid volumes using conditional logistic regression. Results: Distances between the occipital lobes, calcarine sulci and between the skull and V1, V2 and V3a did not differ between patients with migraine aura with headache and patients with migraine aura without headache. We found no differences in corticospinal fluid volumes between groups. Conclusion: We found no indication for a connection between visual migraine aura and headache based on cortico-cortical, cortex-to-skull distances, or corticospinal fluid volumes overlying visual cortical areas. Longitudinal studies with imaging sequences optimized for measuring the cortico-dural distance and a larger sample of patients are needed to further investigate the hypothesis. [ABSTRACT FROM AUTHOR]

Abstract Brain network analysis based on structural and functional magnetic resonance imaging (MRI) is considered as an effective method for consciousness evaluation of hydrocephalus patients, which can also be applied to facilitate the ameliorative effect of lumbar cerebrospinal fluid drainage (LCFD). Automatic brain parcellation is a prerequisite for brain network construction. However, hydrocephalus images usually have large deformations and lesion erosions, which becomes challenging for ensuring effective brain parcellation works. In this paper, we develop a novel and robust method for segmenting brain regions of hydrocephalus images. Our main contribution is to design an innovative inpainting method that can amend the large deformations and lesion erosions in hydrocephalus images, and synthesize the normal brain version without injury. The synthesized images can effectively support brain parcellation tasks and lay the foundation for the subsequent brain network construction work. Specifically, the novelty of the inpainting method is that it can utilize the symmetric properties of the brain structure to ensure the quality of the synthesized results. Experiments show that the proposed brain abnormality inpainting method can effectively aid the brain network construction, and improve the CRS-R score estimation which represents the patient’s consciousness states. Furthermore, the brain network analysis based on our enhanced brain parcellation method has demonstrated potential imaging biomarkers for better interpreting and understanding the recovery of consciousness in patients with secondary hydrocephalus.

IntroductionHeterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence.MethodsOur international working group, funded by the EU Joint Programme-Neurodegenerative Disease Research (JPND), is working toward the production of a reliable, validated, harmonized protocol for segmentation of medial temporal lobe regions. The working group uses a novel postmortem data set and online consensus procedures to ensure validity and facilitate adoption.ResultsThis progress report describes the initial results and milestones that we have achieved to date, including the development of a draft protocol and results from the initial reliability tests and consensus procedures.DiscussionA harmonized protocol will enable the standardization of segmentation methods across laboratories interested in medial temporal lobe research worldwide.

Structural and diffusion kurtosis imaging (DKI) can be used to assess hippocampal macrostructural and microstructural alterations respectively, in Alzheimer's disease (AD) spectrum, spanning from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) and AD. In this study, we explored the diagnostic performance of structural imaging and DKI of the hippocampus in the AD spectrum. Eleven SCD, thirty-seven MCI, sixteen AD, and nineteen age- and sex-matched normal controls (NCs) were included. Bilateral hippocampal volume, mean diffusivity (MD), and mean kurtosis (MK) were obtained. We detected that in AD vs. NCs, the right hippocampal volume showed the most prominent AUC value (AUC = 0.977); in MCI vs. NCs, the right hippocampal MD was the most sensitive discriminator (AUC = 0.819); in SCD vs. NCs, the left hippocampal MK was the most sensitive biomarker (AUC = 0.775). These findings suggest that, in the predementia stage (SCD and MCI), hippocampal microstructural changes are predominant, and the best discriminators are microstructural measurements (left hippocampal MK for SCD and right hippocampal MD for MCI); while in the dementia stage (AD), hippocampal macrostructural alterations are superior, and the best indicator is the macrostructural index (right hippocampal volume). [ABSTRACT FROM AUTHOR]

Purpose: To develop a new approach to 3D gradient echo‐based anatomical imaging of the neonatal brain with a substantially shorter scan time than standard 3D fast spin echo (FSE) methods, while maintaining a high SNR. Methods: T2‐prepration was employed immediately prior to image acquisition of 3D balanced steady‐state free precession (bSSFP) with a single trajectory of center‐out k‐space view ordering, which requires no magnetization recovery time between imaging segments during the scan. This approach was compared with 3D FSE, 2D single‐shot FSE, and product 3D bSSFP imaging in numerical simulations, plus phantom and in vivo experiments. Results: T2‐prepared 3D bSSFP generated image contrast of gray matter, white matter, and CSF very similar to that of reference T2‐weighted imaging methods, without major image artifacts. Scan time of T2‐prepared 3D bSSFP was remarkably shorter compared to 3D FSE, whereas SNR was comparable to that of 3D FSE and higher than that of 2D single‐shot FSE. Specific absorption rate of T2‐prepared 3D bSSFP remained within the safety limit. Determining an optimal imaging flip angle of T2‐prepared 3D bSSFP was critical to minimizing blurring of images. Conclusion: T2‐prepared 3D bSSFP offers an alternative method for anatomical imaging of the neonatal brain with dramatically reduced scan time compared to standard 3D FSE and higher SNR than 2D single‐shot FSE. [ABSTRACT FROM AUTHOR]

The development of three-photon microscopy (3PM) has greatly expanded the capability of imaging deep within biological tissues, enabling neuroscientists to visualize the structure and activity of neuronal populations with greater depth than two-photon imaging. In this review, we outline the history and physical principles of 3PM technology. We cover the current techniques for improving the performance of 3PM. Furthermore, we summarize the imaging applications of 3PM for various brain regions and species. Finally, we discuss the future of 3PM applications for neuroscience. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common age-related neurodegenerative disease with cardinal motor symptoms. In addition to motor symptoms, PD is a heterogeneous disease accompanied by many non-motor symptoms that dominate the clinical manifestations in different stages or subtypes of PD, such as cognitive impairments. The heterogeneity of PD suggests widespread brain structural changes, and axonal involvement appears to be critical to the pathophysiology of PD. As α-synuclein pathology has been suggested to cause axonal changes followed by neuronal degeneration, diffusion tensor imaging (DTI) as an in vivo imaging technique emerges to characterize early detectable white matter changes due to PD. Here, we reviewed the past 5-year literature to show how DTI has helped identify axonal abnormalities at different PD stages or in different PD subtypes and atypical parkinsonism. We also showed the recent clinical utilities of DTI tractography in interventional treatments such as deep brain stimulation (DBS). Mounting evidence supported by multisite DTI data suggests that DTI along with the advanced analytic methods, can delineate dynamic pathophysiological processes from the early to late PD stages and differentiate distinct structural networks affected in PD and other parkinsonism syndromes. It indicates that DTI, along with recent advanced analytic methods, can assist future interventional studies in optimizing treatments for PD patients with different clinical conditions and risk profiles. [ABSTRACT FROM AUTHOR]

Brain network analysis based on structural and functional magnetic resonance imaging (MRI) is considered as an effective method for consciousness evaluation of hydrocephalus patients, which can also be applied to facilitate the ameliorative effect of lumbar cerebrospinal fluid drainage (LCFD). Automatic brain parcellation is a prerequisite for brain network construction. However, hydrocephalus images usually have large deformations and lesion erosions, which becomes challenging for ensuring effective brain parcellation works. In this paper, we develop a novel and robust method for segmenting brain regions of hydrocephalus images. Our main contribution is to design an innovative inpainting method that can amend the large deformations and lesion erosions in hydrocephalus images, and synthesize the normal brain version without injury. The synthesized images can effectively support brain parcellation tasks and lay the foundation for the subsequent brain network construction work. Specifically, the novelty of the inpainting method is that it can utilize the symmetric properties of the brain structure to ensure the quality of the synthesized results. Experiments show that the proposed brain abnormality inpainting method can effectively aid the brain network construction, and improve the CRS-R score estimation which represents the patient's consciousness states. Furthermore, the brain network analysis based on our enhanced brain parcellation method has demonstrated potential imaging biomarkers for better interpreting and understanding the recovery of consciousness in patients with secondary hydrocephalus. [ABSTRACT FROM AUTHOR]

The transition zone between the North and the Central Eastern Desert of Egypt has been investigated using airborne magnetic and radiometric data to better characterize the subsurface structures, the tectonic framework, and mineral occurrences in the area. The magnetic data were subjected to several filtering and depth estimation techniques including edge detectors, Euler deconvolution, 2D forward modeling and 3D inversion. Statistical trend analysis of the lineaments obtained from geological and filtered magnetic maps shows that the major tectonic trends are NNE–SSW, NE–SW, and NW–SE, in addition to less predominant ENE–WSW and N–S trends. Two parallel shear zones trending NE–SW were detected. The causative magnetic structures were imaged at depths varying from the surface down to 2200 m. A number of strong uranium anomalies associated with Younger Granites and Dakhla, Duwi, and Quseir formations were identified which are worth being considered for further ground investigations. [ABSTRACT FROM AUTHOR]

The ineligible role of the caudate nucleus in sleep has been implicated. Previous literature showed that the caudate volume is associated with longer habitual sleep duration in older adults. However, the association between sleep duration and caudate volume remains unknown in the younger population. In this study, we examined the caudate volume in youth to older adults (10 to 85 years old) with a greater sample size (N = 464). The volumetric size of the caudate nucleus showed significantly positive association with habitual sleep duration, especially in younger population. Sleep duration showed a significant association with executive function performance. However, caudate volume did not significantly predict executive function. Our results suggested that sleep duration is associated with the caudate volume and executive function. It is also suggested that there are some external mechanisms that modulate executive function which prevent the caudate-sleep relation's effect on executive function. [ABSTRACT FROM AUTHOR]

Tissue-resident mononuclear phagocytes (MPs) are an abundant cell population whose localization in situ reflects their identity. To enable assessment of their heterogeneity, we developed the red/green/blue (RGB)-Mac mouse based upon combinations of Cx3cr1 and Csf1r reporter transgenes, providing a complete visualization of their spatial organization in situ. 3D-multi-photon imaging for spatial mapping and spectral cytometry employing the three markers in combination distinguished tissue-associated monocytes, tissue-specific macrophages, and three subsets of connective-tissue-associated MPs, including CCR2+ monocyte-derived cell, CX3CR1+, and FOLR2+ interstitial subsets, associated with distinct sub-anatomic territories. These populations were selectively reduced by blockade of CSF1, CSF2, CCR2, and CX3CR1 and efficiently reconstitute their spatial distribution after transient myelo-ablation, suggesting an autonomous regulatory environment. Our findings emphasize the organization of the MP compartment at the sub-anatomic level under steady-state conditions, thereby providing a holistic understanding of their relative heterogeneity across different tissues. [Display omitted] • Tissue-resident macrophage subsets are associated with distinct sub-anatomic territories • Tissue-resident macrophage subsets harbor distinct molecular dependencies • The RGB-Mac mouse discriminates three common interstitial macrophage subsets across tissues Petit et al. show that the different mononuclear phagocyte subsets in non-lymphoid organs are spatially organized according to distinct sub-territories and depend on different molecular regulators. This spatial mapping provides a better understanding of the diversity of the mononuclear phagocyte system across different tissues. [ABSTRACT FROM AUTHOR]

Background: Autistic traits are commonly viewed as dimensional in nature, and as continuously distributed in the general population. In this respect, the identification of predictive values of markers such as subtle autism-related alterations in brain morphology for parameter values of autistic traits could increase our understanding of this dimensional occasion. However, currently, very little is known about how these traits correspond to alterations in brain morphology in typically developing individuals, particularly during a time period where changes due to brain development processes do not provide a bias. Therefore, in the present study, we analyzed brain volume, cortical thickness (CT) and surface area (SA) in a cohort of 14–15-year-old adolescents (N = 285, female: N = 162) and tested their predictive value for autistic traits, assessed with the social responsiveness scale (SRS) two years later at the age of 16–17 years, using a regression-based approach. We found that autistic traits were significantly predicted by volumetric changes in the amygdala (r = 0.181), cerebellum (r = 0.128) and hippocampus (r = −0.181, r = −0.203), both in boys and girls. Moreover, the CT of the superior frontal region was negatively correlated (r = −0.144) with SRS scores. Furthermore, we observed a significant association between the SRS total score and smaller left putamen volume, specifically in boys (r = −0.217), but not in girls. Our findings suggest that neural correlates of autistic traits also seem to lie on a continuum in the general population, are determined by limbic–striatal neuroanatomical brain areas, and are partly dependent on sex. As we imaged adolescents from a large population-based cohort within a small age range, these data may help to increase the understanding of autistic-like occasions in otherwise typically developing individuals. [ABSTRACT FROM AUTHOR]

Antisocial and aggressive behaviors show considerable heritability and are central to disruptive behavior disorders (DBDs), but are also frequently observed in attention deficit hyperactivity disorder (ADHD). While the amygdala is implicated as a key neural structure, it remains unclear whether common genetic variants underlie this brain-behavior association. We hypothesized that polygenic (risk) scores for antisocial and aggressive behaviors (ASB-PRS) would be related to amygdala morphology. Using the Broad Antisocial Behavior Consortium genome-wide association study (GWAS; mostly population based cohorts), we calculated ASB-PRS in the NeuroIMAGE I ADHD case-control sample with varying levels of DBD symptomatology (n=679 from 379 families, aged 7 – 29). We first investigated associations of several ASB-PRS p value thresholds with the presence of DBD symptoms and self-reported antisocial behavior (ASB) to determine the threshold for further analyses. This PRS was then related to amygdala volume and shape using regression and vertex-wise analyses. Our results showed associations of ASB-PRS with the presence of DBD symptoms, self-reported ASB, and left basolateral amygdala shape, independent of ADHD symptom severity and ADHD-PRS, with a relative outward displacement of the vertices. No associations of ASB-PRS, DBD symptoms or self-reported ASB with amygdala volume were found. Our results indicate that genetic risk for antisocial and aggressive behaviors is related to amygdala shape alterations, and point to genetic sharing across different DBD and ASB and aggression-related phenotypes as a spectrum of genetically related quantitative traits. Additionally, our findings support the utility of vertex-based shape analyses in genetic studies of ASB, aggression, and DBDs. [ABSTRACT FROM AUTHOR]

This paper investigated cortical folding in Huntington's disease to understand how disease progression impacts the surface of the cortex. Cortical morphometry changes in eight gyral based regions of interest (i.e. the left and right hemispheres of the lateral occipital, precentral, superior frontal and rostral middle gyri) were examined. We used existing neuroimaging data from IMAGE-HD, comprising 26 pre-symptomatic, 26 symptomatic and 24 healthy control individuals at three separate time points (baseline, 18-month, 30-month). Local gyrification index and cortical thickness were derived as the measures of cortical morphometry using FreeSurfer 6.0's longitudinal pipeline. The gyral based regions of interest were identified using the Desikan-Killiany Atlas. A Group by Time repeated measures ANCOVA was conducted for each region of interest. We found significantly lower LGI at a group level in the right hemisphere lateral occipital region and both hemispheres of the precentral region; as well as significantly reduced cortical thickness at a group level in both hemispheres of the lateral occipital and precentral regions and the right hemisphere of the superior frontal region. We also found a Group by Time interaction for Local gyrification index in the right hemisphere lateral occipital region. This change was largely driven by a significant decrease in the symptomatic group between baseline and 18-months. Additionally, lower local gyrification index and cortical thickness were associated with higher disease burden score. These findings demonstrate that significant longitudinal decline in right hemisphere local gyrification index is evident during manifest disease in lateral occipital cortex and that these changes are more profound in individuals with greater disease burden score. [ABSTRACT FROM AUTHOR]

Age-related changes in cognition are partially mediated by the presence of neuropathology and neurodegeneration. This manuscript evaluates the degree to which biomarkers of Alzheimer's disease, (AD) neuropathology and longitudinal changes in brain structure, account for age-related differences in cognition. Data from the AD Neuroimaging Initiative (n = 1012) were analyzed, including individuals with normal cognition and mild cognitive impairment. Parallel process mixed effects regression models characterized longitudinal trajectories of cognitive variables and time-varying changes in brain volumes. Baseline age was associated with both memory and executive function at baseline (p's < 0.001) and change in memory and executive function performances over time (p's < 0.05). After adjusting for clinical diagnosis, baseline, and longitudinal changes in brain volume, and baseline levels of cerebrospinal fluid biomarkers, age effects on change in episodic memory and executive function were fully attenuated, age effects on baseline memory were substantially attenuated, but an association remained between age and baseline executive function. Results support previous studies that show that age effects on cognitive decline are fully mediated by disease and neurodegeneration variables but also show domain-specific age effects on baseline cognition, specifically an age pathway to executive function that is independent of brain and disease pathways.

BackgroundThe presence of white matter hyperintensities (WMHs) in migraine is well-documented, but the location of WMH in patients with migraine is insufficiently researched. This study assessed WMH in patients with migraine using a modified version of the Scheltens visual rating scale, a semiquantitative scale for categorizing WMH in periventricular, lobar, basal ganglia, and infratentorial regions.MethodsIn total, 263 patients with migraine (31 men and232 women) enrolled in the American Registry for Migraine Research (ARMR) from Mayo Clinic Arizona and who had clinical brain magnetic resonance imaging (MRI) were included in this study. Those with imaging evidence for gross anatomical abnormalities other than WMHs were excluded. A board-certified neuroradiologist identified WMHs on axial T2 and fluid-attenuated inversion recovery (FLAIR) sequences. WMHs were characterized via manual inspection and categorized according to the scale's criteria.ResultsResults showed that 95 patients (36.1%, mean age: 41.8 years) had no WMHs on axial T2 and FLAIR imaging and 168 patients (63.9%, mean age: 51.4 year) had WMHs. Of those with WMHs, 94.1% (n = 158) had lobar hyperintensities (frontal: 148/158, 93.7%; parietal: 57/158, 36.1%; temporal: 35/158, 22.1%; and occipital: 9/158, 5.7%), 13/168, 7.7% had basal ganglia WMHs, 49/168, 29.1% had periventricular WMHs, and 17/168, 10.1% had infratentorial WMHs. In addition, 101/168 patients (60.1%) had bilateral WMHs and 67/168 (39.9%) had unilateral WMHs (34 right hemisphere/33 left hemisphere).DiscussionAmong ARMR participants who were enrolled by Mayo Clinic Arizona and who had clinical brain MRIs, nearly two-thirds had WMHs. The WMHs were the most common in the frontal lobes. Describing the features of WMHs in those with migraine, and comparing them with WMHs attributable to other etiologies, might be useful for developing classifiers that differentiate between migraine-specific WMH and other causes of WMH.

Structural and diffusion kurtosis imaging (DKI) can be used to assess hippocampal macrostructural and microstructural alterations respectively, in Alzheimer’s disease (AD) spectrum, spanning from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) and AD. In this study, we explored the diagnostic performance of structural imaging and DKI of the hippocampus in the AD spectrum. Eleven SCD, thirty-seven MCI, sixteen AD, and nineteen age- and sex-matched normal controls (NCs) were included. Bilateral hippocampal volume, mean diffusivity (MD), and mean kurtosis (MK) were obtained. We detected that in AD vs. NCs, the right hippocampal volume showed the most prominent AUC value (AUC = 0.977); in MCI vs. NCs, the right hippocampal MD was the most sensitive discriminator (AUC = 0.819); in SCD vs. NCs, the left hippocampal MK was the most sensitive biomarker (AUC = 0.775). These findings suggest that, in the predementia stage (SCD and MCI), hippocampal microstructural changes are predominant, and the best discriminators are microstructural measurements (left hippocampal MK for SCD and right hippocampal MD for MCI); while in the dementia stage (AD), hippocampal macrostructural alterations are superior, and the best indicator is the macrostructural index (right hippocampal volume).

Objectives: Abnormal beliefs and delusions have been reported in some people with dementia, however, the prevalence of delusions, and their neurocognitive basis has been underexplored. This study aimed to examine the presence, severity, content and neural correlates of delusions in a large, well-characterised cohort of dementia patients using a transdiagnostic, cross-sectional approach.Methods: Four-hundred and eighty-seven people with dementia were recruited: 102 Alzheimer's disease, 136 behavioural-variant frontotemporal dementia, 154 primary progressive aphasia, 29 motor neurone disease, 46 corticobasal syndrome, 20 progressive supranuclear palsy. All patients underwent neuropsychological assessment and brain magnetic resonance imaging, and the Neuropsychiatric Inventory was conducted with an informant, by an experienced clinician.Results: In our cohort, 48/487 patients (10.8%) had delusions. A diagnosis of behavioural-variant frontotemporal dementia (18.4%) and Alzheimer's disease (11.8%) were associated with increased risk of delusions. A positive gene mutation was observed in 11/27 people with delusions. Individuals with frequent delusions performed worse on the Addenbrooke's Cognitive Examination (p = 0.035), particularly on the orientation/attention (p = 0.022) and memory (p = 0.013) subtests. Voxel-based morphometry analyses found that increased delusional psychopathology was associated with reduced integrity of the right middle frontal gyrus, right planum temporale and left anterior temporal pole.Conclusion: Our results demonstrate that delusions are relatively common in dementia and uncover a unique cognitive and neural profile associated with the manifestation of delusions. Clinically, delusions may lead to delayed or misdiagnosis. Our results shed light on how to identify individuals at risk of neuropsychiatric features of dementia, a crucial first step to enable targeted symptom management. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is increasingly used in medical image analysis and has accelerated scientific discoveries across fields of medicine. In this review, we highlight how AI has been applied to neuroimaging in patients with epilepsy to enhance classification of clinical diagnosis, prediction of treatment outcomes, and the understanding of cognitive comorbidities. We outline the strengths and shortcomings of current AI research and the need for future studies using large datasets that test the reproducibility and generalizability of current findings, as well as studies that test the clinical utility of AI approaches. [ABSTRACT FROM AUTHOR]

BackgroundThe oxytocin (OT) system, including receptor epigenetic mechanisms, has been shown to influence emotion processing, especially in females. Whether OT receptor (OXTR) epigenetic alterations occur across psychotic disorders in relation to illness-related disturbances in social cognition and brain anatomy is unknown.MethodsParticipants with affective and nonaffective psychotic disorders (92 women, 75 men) and healthy controls (38 women, 37 men) from the Chicago site of the BSNIP study completed the Penn Emotion Recognition Test (ER-40), a facial emotion recognition task. We measured cytosine methylation at site -934 upstream of the OXTR start codon in DNA from whole blood, and for the first time their relationship with plasma OT levels assessed by enzyme-immunoassay. Volumes of brain regions supporting social cognition were measured from MRI scans using FreeSurfer.ResultsPatients with prototypic schizophrenia features showed higher levels of DNA methylation than those with prototypic bipolar features. Methylation was higher in women than men, and was associated with poorer emotion recognition only in female patients and controls. Greater methylation was associated with smaller volumes in temporal-limbic and prefrontal regions associated previously with social cognition, but only in healthy women and females with schizophrenia.ConclusionDNA methylation of the OXTR site -934 was higher in schizophrenia spectrum than bipolar patients. Among patients, it was linked to behavioral deficits in social cognition and neuroanatomic structures known to support emotion processing only in schizophrenia spectrum individuals.

The placenta is a highly vascularised organ with unique structural and metabolic complexities. As the primary conduit of fetal support, the placenta mediates transport of oxygen, nutrients, and waste between maternal and fetal blood. Thus, normal placenta anatomy and physiology is absolutely required for maintenance of maternal and fetal health during pregnancy. Moreover, impaired placental health can negatively impact offspring growth trajectories as well as increase the risk of maternal cardiovascular disease later in life. Despite these crucial roles for the placenta, placental disorders, such as preeclampsia, intrauterine growth restriction, and preterm birth, remain incompletely understood. Effective noninvasive imaging and image analysis are needed to advance the obstetrician’s clinical reasoning toolkit and improve the utility of the placenta in interpreting maternal and fetal health trajectories. Current paradigms in placental imaging and image analysis aim to improve the traditional imaging techniques that may be time-consuming, costly, or invasive. In concert with conventional clinical approaches such as ultrasound, advanced imaging modalities can provide insightful information on the structure of placental tissues. Herein, the authors discuss such imaging modalities; their specific applications in structural, vascular, and metabolic analysis of placental health; and emerging frontiers in image analysis research in both preclinical and clinical contexts.

Abstract Background The frequently cited Early Overgrowth Hypothesis of autism spectrum disorder (ASD) postulates that there is overgrowth of the brain in the first 2 years of life, which is followed by a period of arrested growth leading to normalized brain volume in late childhood and beyond. While there is consistent evidence for early brain overgrowth, there is mixed evidence for normalization of brain volume by middle childhood. The outcome of this debate is important to understanding the etiology and neurodevelopmental trajectories of ASD. Methods Brain volume was examined in two very large single-site samples of children, adolescents, and adults. The primary sample comprised 456 6–25-year-olds (ASD n = 240, typically developing controls (TDC) n = 216), including a large number of females (n = 102) and spanning a wide IQ range (47–158). The replication sample included 175 males. High-resolution T1-weighted anatomical MRI images were examined for group differences in total brain, cerebellar, ventricular, gray, and white matter volumes. Results The ASD group had significantly larger total brain, cerebellar, gray matter, white matter, and lateral ventricular volumes in both samples, indicating that brain volume remains enlarged through young adulthood, rather than normalizing. There were no significant age or sex interactions with diagnosis in these measures. However, a significant diagnosis-by-IQ interaction was detected in the larger sample, such that increased brain volume was related to higher IQ in the TDCs, but not in the ASD group. Regions-of-significance analysis indicated that total brain volume was larger in ASD than TDC for individuals with IQ less than 115, providing a potential explanation for prior inconsistent brain size results. No relationships were found between brain volume and measures of autism symptom severity within the ASD group. Limitations Our cross-sectional sample may not reflect individual changes over time in brain volume and cannot quantify potential changes in volume prior to age 6. Conclusions These findings challenge the “normalization” prediction of the brain overgrowth hypothesis by demonstrating that brain enlargement persists across childhood into early adulthood. The findings raise questions about the clinical implications of brain enlargement, since we find that it neither confers cognitive benefits nor predicts increased symptom severity in ASD.

Abstract Introduction Heterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence. Methods Our international working group, funded by the EU Joint Programme–Neurodegenerative Disease Research (JPND), is working toward the production of a reliable, validated, harmonized protocol for segmentation of medial temporal lobe regions. The working group uses a novel postmortem data set and online consensus procedures to ensure validity and facilitate adoption. Results This progress report describes the initial results and milestones that we have achieved to date, including the development of a draft protocol and results from the initial reliability tests and consensus procedures. Discussion A harmonized protocol will enable the standardization of segmentation methods across laboratories interested in medial temporal lobe research worldwide.

Pathogenic copy number variants (CNVs) and aneuploidies alter gene dosage and are associated with neurodevelopmental psychiatric disorders such as autism spectrum disorder and schizophrenia. Brain mechanisms mediating genetic risk for neurodevelopmental psychiatric disorders remain largely unknown, but there is a rapid increase in morphometry studies of CNVs using T1-weighted structural magnetic resonance imaging. Studies have been conducted one mutation at a time, leaving the field with a complex catalog of brain alterations linked to different genomic loci. Our aim was to provide a systematic review of neuroimaging phenotypes across CNVs associated with developmental psychiatric disorders including autism and schizophrenia. We included 76 structural magnetic resonance imaging studies on 20 CNVs at the 15q11.2, 22q11.2, 1q21.1 distal, 16p11.2 distal and proximal, 7q11.23, 15q11-q13, and 22q13.33 (SHANK3) genomic loci as well as aneuploidies of chromosomes X, Y, and 21. Moderate to large effect sizes on global and regional brain morphometry are observed across all genomic loci, which is in line with levels of symptom severity reported for these variants. This is in stark contrast with the much milder neuroimaging effects observed in idiopathic psychiatric disorders. Data also suggest that CNVs have independent effects on global versus regional measures as well as on cortical surface versus thickness. Findings highlight a broad diversity of regional morphometry patterns across genomic loci. This heterogeneity of brain patterns provides insight into the weak effects reported in magnetic resonance imaging studies of cognitive dimension and psychiatric conditions. Neuroimaging studies across many more variants will be required to understand links between gene function and brain morphometry. [ABSTRACT FROM AUTHOR]

A symptom of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is a flat learning profile. Learning slope calculation methods vary, and the optimal method for capturing neuroanatomical changes associated with MCI and early AD pathology is unclear. This study cross-sectionally compared four different learning slope measures from the Rey Auditory Verbal Learning Test (simple slope, regression-based slope, two-slope method, peak slope) to structural neuroimaging markers of early AD neurodegeneration (hippocampal volume, cortical thickness in parahippocampal gyrus, precuneus, and lateral prefrontal cortex) across the cognitive aging spectrum [normal control (NC); (n=198; age=76±5), MCI (n=370; age=75±7), and AD (n=171; age=76±7)] in ADNI. Within diagnostic group, general linear models related slope methods individually to neuroimaging variables, adjusting for age, sex, education, and APOE4 status. Among MCI, better learning performance on simple slope, regression-based slope, and late slope (Trial 2-5) from the two-slope method related to larger parahippocampal thickness (all p-values

Background: Autistic traits are commonly viewed as dimensional in nature, and as continuously distributed in the general population. In this respect, the identification of predictive values of markers such as subtle autism-related alterations in brain morphology for parameter values of autistic traits could increase our understanding of this dimensional occasion. However, currently, very little is known about how these traits correspond to alterations in brain morphology in typically developing individuals, particularly during a time period where changes due to brain development processes do not provide a bias. Therefore, in the present study, we analyzed brain volume, cortical thickness (CT) and surface area (SA) in a cohort of 14–15-year-old adolescents (N = 285, female: N = 162) and tested their predictive value for autistic traits, assessed with the social responsiveness scale (SRS) two years later at the age of 16–17 years, using a regression-based approach. We found that autistic traits were significantly predicted by volumetric changes in the amygdala (r = 0.181), cerebellum (r = 0.128) and hippocampus (r = −0.181, r = −0.203), both in boys and girls. Moreover, the CT of the superior frontal region was negatively correlated (r = −0.144) with SRS scores. Furthermore, we observed a significant association between the SRS total score and smaller left putamen volume, specifically in boys (r = −0.217), but not in girls. Our findings suggest that neural correlates of autistic traits also seem to lie on a continuum in the general population, are determined by limbic–striatal neuroanatomical brain areas, and are partly dependent on sex. As we imaged adolescents from a large population-based cohort within a small age range, these data may help to increase the understanding of autistic-like occasions in otherwise typically developing individuals.

Dementia is a major public health problem with high needs for early detection, efficient treatment, and prognosis evaluation. Social cognition impairment could be an early dementia indicator and can be assessed with emotion recognition evaluation tests. The purpose of this study is to investigate the link between different brain imaging modalities and cognitive status in Mild Cognitive Impairment (MCI) patients, with the goal of uncovering potential physiopathological mechanisms based on social cognition performance. The relationship between the Reading the Mind in the Eyes Test (RMET) and some clinical and biochemical variables ([18 F]FDG PET-CT and anatomical MR parameters, neuropsychological evaluation, and CSF biomarkers) was studied in 166 patients with MCI by using a correlational approach. The RMET correlated with neuropsychological variables, as well as with structural and functional brain parameters obtained from the MR and FDG-PET imaging evaluation. However, significant correlations between the RMET and CSF biomarkers were not found. Different neuroimaging parameters were found to be related to an emotion recognition task in MCI. This analysis identified potential minimally-invasive biomarkers providing some knowledge about the physiopathological mechanisms in MCI. [Display omitted] • The RMET was used to evaluate complex emotion recognition in MCI patients. • The RMET performance was not specific for the AD's biological substrate. • Anatomical and functional correlates were found between RMET and emotional areas. • Social cognition and brain imaging may be useful in early detection of dementia. [ABSTRACT FROM AUTHOR]

Study objectivesTo investigate whether subjective sleep quality is associated with brain volume independent of comorbid psychiatric conditions.DesignCross-sectional.SettingDepartment of Veterans Affairs (VA) Medical Center.ParticipantsOne hundred forty-four Gulf War Veterans (mean age 45 years; range: 31-70 years; 14% female).InterventionsNone.Measurements and resultsTotal cortical, lobar gray matter, and hippocampal volumes were quantified from 1.5 Tesla magnetic resonance images using Freesurfer version 4.5. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Multiple linear regressions were used to determine the association of sleep quality with total and regional brain volumes. The global PSQI score was positively correlated with lifetime and current posttraumatic stress disorder (PTSD) and current depressive symptoms (P < 0.001) and was higher in veterans with Gulf War Illness, trauma exposure, and those using psychotropic medication (P ≤ 0.03). After adjusting for these comorbid variables, age, intracranial volume, and multiple comparisons, global PSQI was inversely associated with total cortical and frontal gray matter volume (adjusted P ≤ 0.03). Within the frontal lobe, total PSQI was inversely associated with the superior and middle frontal, orbitofrontal, anterior cingulate, and frontal pole volumes (adjusted P ≤ 0.02). Examination of the 3-factor structure of the PSQI revealed that the associations were driven by perceived sleep quality.ConclusionsPoorer subjective sleep quality was associated with reduced total cortical and regional frontal lobe volumes independent of comorbid psychiatric conditions. Future work will be needed to examine if effective treatment of disturbed sleep leads to improved structural and functional integrity of the frontal lobes.

Accurate extraction of the cortical brain surface is critical for cortical thickness estimation and a key element to perform multimodal imaging analysis, where different metrics are integrated and compared in a common space. While brain surface extraction has become widespread practice in human studies, several challenges unique to neuroimaging of non-human primates (NHP) have hindered its adoption for the study of macaques. Although, some of these difficulties can be addressed at the acquisition stage, several common artifacts can be minimized through image preprocessing. Likewise, there are several image analysis pipelines for human MRIs, but very few automated methods for extraction of cortical surfaces have been reported for NHPs and none have been tested on data from diverse sources. We present PREEMACS, a pipeline that standardizes the preprocessing of structural MRI images (T1- and T2-weighted) and carries out an automatic surface extraction of the macaque brain. Building upon and extending pre-existing tools, the first module performs volume orientation, image cropping, intensity non-uniformity correction, and volume averaging, before skull-stripping through a convolutional neural network. The second module performs quality control using an adaptation of MRIqc method to extract objective quality metrics that are then used to determine the likelihood of accurate brain surface estimation. The third and final module estimates the white matter (wm) and pial surfaces from the T1-weighted volume (T1w) using an NHP customized version of FreeSurfer aided by the T2-weighted volumes (T2w). To evaluate the generalizability of PREEMACS, we tested the pipeline using 57 T1w/T2w NHP volumes acquired at 11 different sites from the PRIME-DE public dataset. Results showed an accurate and robust automatic brain surface extraction from images that passed the quality control segment of our pipeline. This work offers a robust, efficient and generalizable pipeline for the automatic standardization of MRI surface analysis on NHP.

Background: Craving is the predictor of relapse, and insula cortex (IC) is a critical neural substrate for craving and drug seeking. This study investigated whether IC abnormalities among MA users can detect craving state and predict relapse susceptibility.Methods: A total of 142 subjects with a history of MA dependence completed structural MRI (sMRI) scans, and 30 subjects (10 subjects relapsed) completed 4-month follow-up scans. MA craving was measured by the Visual Analog Scale for Craving. Abnormalities of IC gray matter volume (GMV) between the subjects with and without craving were investigated by voxel-based morphometry (VBM). The receiver operating characteristic (ROC) analysis was performed for the region-of-interest (ROI) of IC GMV to assess the diagnostic accuracy.Results: By comparing whole-brain volume maps, this study found that subjects without craving (n = 64) had a significantly extensive decrease in IC GMV (family-wise error correction, p < 0.05) than subjects with craving group (n = 78). The ROI of IC GMV had a significantly positive correlation with the craving scores reported by MA users. The ROC analysis showed a good discrimination (area under curve is 0.82/0.80 left/right) for IC GMV between the subjects with and without craving. By selecting Youden index cut-off point from whole model group, calculated sensitivity/specificity was equal to 78/70% and 70/75% for left and right IC, respectively. By applying the above optimal cut-off values to 30 follow-up subjects as validations, the results showed a similar sensitivity (73–80%) and specificity (73–80%) for detecting craving state as model group. For predicting relapse susceptibility, the sensitivity (50–55%) was low and the specificity (80–90%) was high.Conclusions: Our study provides the first evidence that sMRI may be used to diagnosis the craving state in MA users based on optimal cut-off values, which could be served as MRI bio-markers and an objective measure of craving state.