Longitudinal Changes in Iron and Myelination Within Ischemic Lesions Associate With Neurological Outcomes: A Pilot Study.

BACKGROUND: Combined quantitative susceptibility mapping and R2* relaxometry can distinguish iron and myelin components in ischemic lesions. We aimed to investigate whether longitudinal changes in magnetic susceptibility and R2* values within ischemic lesions were associated with neurological outcomes. METHODS: In this single-center prospective study, we included patients, 20 to 90 years of age, who were consecutively admitted to the stroke care unit between August 2020 and March 2022 due to acute ischemic stroke. The participants underwent 2 instances of quantitative susceptibility mapping and R2* relaxometry scanning before and after stroke rehabilitation. We compared the changes in these quantitative measures across different subtypes of acute ischemic stroke. Multiple linear regression models were used to investigate the associations between the National Institutes of Health Stroke Scale scores and the mean magnetic susceptibility and R2* values in ischemic lesions. RESULTS: Among a total of 112 patients with acute ischemic stroke, 32 participants (aged 73.3±9.4 years; 20 men and 12 women) were evaluated. The median time from stroke onset to the first imaging was 5 days and that to the second imaging was 102 days. The changes in magnetic susceptibility values of branch atheromatous disease were higher than those of cardioembolism (mean difference, 0.018 [95% CI, 0.009-0.027] ppm; P<0.001) and lacunar (mean difference, 0.013 [95% CI, 0.005-0.020] ppm; P=0.004). Across all patients, the changes in National Institutes of Health Stroke Scale scores were associated with those of magnetic susceptibility values (coefficient, 0.311 [95% CI, 0.098-0.520]; P=0.017) but not with R2* values (coefficient, 0.114 [95% CI, -0.127 to 0.345]; P=0.291). CONCLUSIONS: The longitudinal changes in the magnetic susceptibility values within ischemic lesions were associated with neurological outcomes during the restorative stages poststroke in patients experiencing acute ischemic stroke. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000050719.

Quantification of Diffusion Magnetic Resonance Imaging for Prognostic Prediction of Neonatal Hypoxic-Ischemic Encephalopathy.

Neonatal hypoxic-ischemic encephalopathy (HIE) is the leading cause of acquired neonatal brain injury with the risk of developing serious neurological sequelae and death. An accurate and robust prediction of short- and long-term outcomes may provide clinicians and families with fundamental evidence for their decision-making, the design of treatment strategies, and the discussion of developmental intervention plans after discharge. Diffusion tensor imaging (DTI) is one of the most powerful neuroimaging tools with which to predict the prognosis of neonatal HIE by providing microscopic features that cannot be assessed by conventional magnetic resonance imaging (MRI). DTI provides various scalar measures that represent the properties of the tissue, such as fractional anisotropy (FA) and mean diffusivity (MD). Since the characteristics of the diffusion of water molecules represented by these measures are affected by the microscopic cellular and extracellular environment, such as the orientation of structural components and cell density, they are often used to study the normal developmental trajectory of the brain and as indicators of various tissue damage, including HIE-related pathologies, such as cytotoxic edema, vascular edema, inflammation, cell death, and Wallerian degeneration. Previous studies have demonstrated widespread alteration in DTI measurements in severe cases of HIE and more localized changes in neonates with mild-to-moderate HIE. In an attempt to establish cutoff values to predict the occurrence of neurological sequelae, MD and FA measurements in the corpus callosum, thalamus, basal ganglia, corticospinal tract, and frontal white matter have proven to have an excellent ability to predict severe neurological outcomes. In addition, a recent study has suggested that a data-driven, unbiased approach using machine learning techniques on features obtained from whole-brain image quantification may accurately predict the prognosis of HIE, including for mild-to-moderate cases. Further efforts are needed to overcome current challenges, such as MRI infrastructure, diffusion modeling methods, and data harmonization for clinical application. In addition, external validation of predictive models is essential for clinical application of DTI to prognostication.

Multi-modal multi-resolution atlas of the human neonatal cerebral cortex based on microstructural similarity.

The neonatal period is a critical window for the development of the human brain and may hold implications for the long-term development of cognition and disorders. Multi-modal connectome studies have revealed many important findings underlying the adult brain but related studies were rare in the early human brain. One potential challenge is the lack of an appropriate and unbiased parcellation that combines structural and functional information in this population. Using 348 multi-modal MRI datasets from the developing human connectome project, we found that the information fused from the structural, diffusion, and functional MRI was relatively stable across MRI features and showed high reproducibility at the group level. Therefore, we generated automated multi-resolution parcellations (300 - 500 parcels) based on the similarity across multi-modal features using a gradient-based parcellation algorithm. In addition, to acquire a parcellation with high interpretability, we provided a manually delineated parcellation (210 parcels), which was approximately symmetric, and the adjacent areas around each boundary were statistically different in terms of the integrated similarity metric and at least one kind of original features. Overall, the present study provided multi-resolution and neonate-specific parcellations of the cerebral cortex based on multi-modal MRI properties, which may facilitate future studies of the human connectome in the early development period.

The Japan Monkey Centre Primates Brain Imaging Repository of high-resolution postmortem magnetic resonance imaging: The second phase of the archive of digital records.

A comparison of neuroanatomical features of the brain between humans and our evolutionary relatives, nonhuman primates, is key to understanding the human brain system and the neural basis of mental and neurological disorders. Although most comparative MRI studies of human and nonhuman primate brains have been based on brains of primates that had been used as subjects in experiments, it is essential to investigate various species of nonhuman primates in order to elucidate and interpret the diversity of neuroanatomy features among humans and nonhuman primates. To develop a research platform for this purpose, it is necessary to harmonize the scientific contributions of studies with the standards of animal ethics, animal welfare, and the conservation of brain information for long-term continuation of the field. In previous research, we first developed a gated data-repository of anatomical images obtained using 9.4-T ex vivo MRI of postmortem brain samples from 12 nonhuman primate species, and which are stored at the Japan Monkey Centre. In the present study, as a second phase, we released a collection of T2-weighted images and diffusion tensor images obtained in nine species: white-throated capuchin, Bolivian squirrel monkey, stump-tailed macaque, Tibet monkey, Sykes' monkey, Assamese macaque, pig-tailed macaque, crested macaque, and chimpanzee. Our image repository should facilitate scientific discoveries in the field of comparative neuroscience. This repository can also promote animal ethics and animal welfare in experiments with nonhuman primate models by optimizing methods for in vivo and ex vivo MRI scanning of brains and supporting veterinary neuroradiological education. In addition, the repository is expected to contribute to conservation, preserving information about the brains of various primates, including endangered species, in a permanent digital form.

APOE ɛ4 dose associates with increased brain iron and ß-amyloid via blood-brain barrier dysfunction.

OBJECTIVE: To examine the effect of apolipoprotein E (APOE) ɛ4 dose on blood-brain barrier (BBB) clearance function, evaluated using an advanced MRI technique and analyse its correlation with brain iron and ß-amyloid accumulation in the early stages of the Alzheimer's continuum. METHODS: In this single-centre observational prospective cohort study, 24 APOE ɛ4 non-carriers, 22 heterozygotes and 20 homozygotes in the early stages of the Alzheimer's continuum were scanned with diffusion-prepared arterial spin labelling, which estimates the water exchange rate across the BBB (kw). Participants also underwent quantitative susceptibility mapping, [11C]Pittsburgh compound B-positron emission tomography and neuropsychological testing. Using an atlas-based approach, we compared the regional kw of the whole brain among the groups and analysed its correlation with the neuroradiological and neuropsychological findings. RESULTS: The BBB kw values in the neocortices differed significantly among the groups (APOE ɛ4 non-carriers>heterozygotes>homozygotes). These values correlated with brain iron levels (frontal lobe: r=-0.476, 95% CI=-0.644 to -0.264, p=0.011; medial temporal lobe: r=-0.455, 95% CI=-0.628 to -0.239, p=0.017), ß-amyloid loads (frontal lobe: r=-0.504, 95% CI=-0.731 to -0.176, p=0.015; medial temporal lobe: r=-0.452, 95% CI=-0.699 to -0.110, p=0.036) and neuropsychological scores, after adjusting for age, sex and APOE ɛ4 dose. INTERPRETATION: Our results suggest that an increased APOE ɛ4 dose is associated with decreased effective brain-waste clearance, such as iron and ß-amyloid, through the BBB.

A Machine Learning-Based Approach to Discrimination of Tauopathies Using [18 F]PM-PBB3 PET Images.

BACKGROUND: We recently developed a positron emission tomography (PET) probe, [18 F]PM-PBB3, to detect tau lesions in diverse tauopathies, including mixed three-repeat and four-repeat (3R + 4R) tau fibrils in Alzheimer's disease (AD) and 4R tau aggregates in progressive supranuclear palsy (PSP). For wider availability of this technology for clinical settings, bias-free quantitative evaluation of tau images without a priori disease information is needed. OBJECTIVE: We aimed to establish tau PET pathology indices to characterize PSP and AD using a machine learning approach and test their validity and tracer capabilities. METHODS: Data were obtained from 50 healthy control subjects, 46 patients with PSP Richardson syndrome, and 37 patients on the AD continuum. Tau PET data from 114 regions of interest were subjected to Elastic Net cross-validation linear classification analysis with a one-versus-the-rest multiclass strategy to obtain a linear function that discriminates diseases by maximizing the area under the receiver operating characteristic curve. We defined PSP- and AD-tau scores for each participant as values of the functions optimized for differentiating PSP (4R) and AD (3R + 4R), respectively, from others. RESULTS: The discriminatory ability of PSP- and AD-tau scores assessed as the area under the receiver operating characteristic curve was 0.98 and 1.00, respectively. PSP-tau scores correlated with the PSP rating scale in patients with PSP, and AD-tau scores correlated with Mini-Mental State Examination scores in healthy control-AD continuum patients. The globus pallidus and amygdala were highlighted as regions with high weight coefficients for determining PSP- and AD-tau scores, respectively. CONCLUSIONS: These findings highlight our technology's unbiased capability to identify topologies of 3R + 4R versus 4R tau deposits. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Quantitative Susceptibility Mapping of Brain Iron and ß-Amyloid in MRI and PET Relating to Cognitive Performance in Cognitively Normal Older Adults.

Background For individuals with mild cognitive impairment (MCI) or dementia, elevated brain iron together with ß-amyloid is associated with lower cognitive functioning. But this needs further investigation among cognitively normal older adults. Purpose To investigate via quantitative susceptibility mapping (QSM) in MRI and PET how cerebral iron together with ß-amyloid affects cognition among cognitively normal older adults. Materials and Methods In this secondary analysis of a prospective study, cognitively normal older adults underwent QSM MRI to measure brain iron. A majority underwent PET to measure cerebral ß-amyloid within 30 days of MRI. Multiple linear regression analyses were performed for 12 cortical and subcortical gray matter regions to assess the effect of brain iron on cognitive functions. Voxel-based analyses investigated the associations between tissue iron and ß-amyloid load and their relationship to cognitive performance. Results Evaluated were 150 cognitively normal older adults (mean age, 69 years ± 8 [standard deviation]; 93 women). Of 150, 97 underwent PET; 22 of the 97 (mean age, 71 years ± 6; 13 women) were positive for ß-amyloid. In all participants, brain iron content in the hippocampus negatively correlated with global cognitive composite score (standardized ß = -0.24; 95% CI: -0.40, -0.07; P = .005). In the PET subgroup, brain iron in the hippocampus negatively correlated with episodic memory (ß = -0.24; 95% CI: -0.40, -0.08; P = .004) and visuospatial score (ß = -0.34; 95% CI: -0.56, -0.12; P = .003) independent of ß-amyloid burden. Both negative and positive correlations between brain iron and ß-amyloid were observed in the PET subgroup, revealing clusters where brain iron content negatively correlated with ß-amyloid and global cognitive scores (eg, in the frontal cortex: ß = -0.13; 95% CI: -0.23, -0.02; P = .02). No clusters showed associations between ß-amyloid and global cognition. Conclusion Among cognitively normal older adults, quantitative susceptibility mapping in MRI and PET indicated that elevated cerebral iron load was related to lower cognitive performance independent of ß-amyloid. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Chiang in this issue.

The association of neuropsychiatric symptoms with regional brain volumes from patients in a tertiary multi-disciplinary memory clinic.

BACKGROUND: To examine the interaction between structural brain volume measures derived from a clinical magnetic resonance imaging (MRI) and occurrence of neuropsychiatric symptoms (NPS) in outpatient memory clinic patients. METHODS: Clinical and neuroimaging data were collected from the medical records of outpatient memory clinic patients who were seen by neurologists, geriatric neuropsychiatrists, and geriatricians. MRI scan acquisition was carried out on a 3 T Siemens Verio scanner at Johns Hopkins Bayview Medical Center. Image analyses used an automated multi-label atlas fusion method with a geriatric atlas inventory to generate 193 anatomical regions from which volumes were measured. Regions of interest were generated a priori based on previous literature review of NPS in dementia. Regional volumes for agitation, apathy, and delusions were carried forward in a linear regression analysis. RESULTS: Seventy-two patients had clinical and usable neuroimaging data that were analyzed and grouped by Mini-Mental State Exam (MMSE). Neuropsychiatric Inventory Questionnaire (NPI-Q) agitation was inversely associated with rostral anterior cingulate cortex (ACC) bilaterally and left subcallosal ACC volumes in the moderate severity group. Delusions were positively associated with left ACC volumes in both severe and mild groups but inversely associated with the right dorsolateral prefrontal cortex (DLPFC) in the moderate subgroup. CONCLUSIONS: Agitation, apathy, and delusions are associated with volumes of a priori selected brain regions using clinical data and clinically acquired MRI scans. The ACC is an anatomic region common to these symptoms, particularly agitation and delusions, which closely mirror the findings of research-quality studies and suggest its importance as a behavioral hub.

Developing Treatments for Alzheimer's and Related Disorders with Precision Medicine: A Vision.

Precision medicine, also known as personalized medicine, is concerned with finding the right treatment for the right patient at the right time. It is a way of thinking focused on parsing heterogeneity ultimately down to the level of the individual. Its main mission is to identify characteristics of heterogeneous clinical conditions so as to target tailored therapies to individuals. Precision Medicine however is not an agnostic collection of all manner of clinical, genetic and other biologic data in select cohorts. This is an important point. Simply collecting as much information as possible on individuals without applying this way of thinking should not be considered Precision Medicine.

Microstructural brain abnormalities in HIV+ individuals with or without chronic marijuana use.

OBJECTIVE: Cognitive deficits and microstructural brain abnormalities are well documented in HIV-positive individuals (HIV+). This study evaluated whether chronic marijuana (MJ) use contributes to additional cognitive deficits or brain microstructural abnormalities that may reflect neuroinflammation or neuronal injury in HIV+. METHOD: Using a 2 × 2 design, 44 HIV+ participants [23 minimal/no MJ users (HIV+), 21 chronic active MJ users (HIV + MJ)] were compared to 46 seronegative participants [24 minimal/no MJ users (SN) and 22 chronic MJ users (SN + MJ)] on neuropsychological performance (7 cognitive domains) and diffusion tensor imaging metrics, using an automated atlas to assess fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities, in 18 cortical and 4 subcortical brain regions. RESULTS: Compared to SN and regardless of MJ use, the HIV+ group had lower FA and higher diffusivities in multiple white matter and subcortical structures (p < 0.001-0.050), as well as poorer cognition in Fluency (p = 0.039), Attention/Working Memory (p = 0.009), Learning (p = 0.014), and Memory (p = 0.028). Regardless of HIV serostatus, MJ users had lower AD in uncinate fasciculus (p = 0.024) but similar cognition as nonusers. HIV serostatus and MJ use showed an interactive effect on mean diffusivity in the right globus pallidus but not on cognitive function. Furthermore, lower FA in left anterior internal capsule predicted poorer Fluency across all participants and worse Attention/Working Memory in all except SN subjects, while higher diffusivities in several white matter tracts also predicted lower cognitive domain Z-scores. Lastly, MJ users with or without HIV infection showed greater than normal age-dependent FA declines in superior longitudinal fasciculus, external capsule, and globus pallidus. CONCLUSIONS: Our findings suggest that, except in the globus pallidus, chronic MJ use had no additional negative influence on brain microstructure or neurocognitive deficits in HIV+ individuals. However, lower AD in the uncinate fasciculus of MJ users suggests axonal loss in this white matter tract that connects to cannabinoid receptor rich brain regions that are involved in verbal memory and emotion. Furthermore, the greater than normal age-dependent FA declines in the white matter tracts and globus pallidus in MJ users suggest that older chronic MJ users may eventually have lesser neuronal integrity in these brain regions.

Baby brain atlases.

The baby brain is constantly changing due to its active neurodevelopment, and research into the baby brain is one of the frontiers in neuroscience. To help guide neuroscientists and clinicians in their investigation of this frontier, maps of the baby brain, which contain a priori knowledge about neurodevelopment and anatomy, are essential. "Brain atlas" in this review refers to a 3D-brain image with a set of reference labels, such as a parcellation map, as the anatomical reference that guides the mapping of the brain. Recent advancements in scanners, sequences, and motion control methodologies enable the creation of various types of high-resolution baby brain atlases. What is becoming clear is that one atlas is not sufficient to characterize the existing knowledge about the anatomical variations, disease-related anatomical alterations, and the variations in time-dependent changes. In this review, the types and roles of the human baby brain MRI atlases that are currently available are described and discussed, and future directions in the field of developmental neuroscience and its clinical applications are proposed. The potential use of disease-based atlases to characterize clinically relevant information, such as clinical labels, in addition to conventional anatomical labels, is also discussed.

Age-specific optimization of T1-weighted brain MRI throughout infancy.

The infant brain undergoes drastic morphological and functional development during the first year of life. Three-dimensional T1-weighted Magnetic Resonance Imaging (3D T1w-MRI) is a major tool to characterize the brain anatomy, which however, manifests inherently low and rapidly changing contrast between white matter (WM) and gray matter (GM) in the infant brains (0-12 month-old). Despite the prior efforts made to maximize tissue contrast in the neonatal brains (≤1 months), optimization of imaging methods in the rest of the infancy (1-12 months) is not fully addressed, while brains in the latter period exhibit even more challenging contrast. Here, we performed a systematic investigation to improve the contrast between cortical GM and subcortical WM throughout the infancy. We first performed simultaneous T1 and proton density mapping in a normally developing infant cohort at 3T (n = 57). Based on the evolution of T1 relaxation times, we defined three age groups and simulated the relative tissue contrast between WM and GM in each group. Age-specific imaging strategies were proposed according to the Bloch simulation: inversion time (TI) around 800 ms for the 0-3 month-old group, dual TI at 500 ms and 700 ms for the 3-7 month-old group, and TI around 700 ms for 7-12 month-old group, using a centrically encoded 3D-MPRAGE sequence at 3T. Experimental results with varying TIs in each group confirmed improved contrast at the proposed optimal TIs, even in 3-7 month-old infants who had nearly isointense contrast. We further demonstrated the advantage of improved relative contrast in segmenting the neonatal brains using a multi-atlas segmentation method. The proposed age-specific optimization strategies can be easily adapted to routine clinical examinations, and the improved image contrast would facilitate quantitative analysis of the infant brain development.

Age-specific gray and white matter DTI atlas for human brain at 33, 36 and 39 postmenstrual weeks.

During the 3rd trimester, dramatic structural changes take place in the human brain, underlying the neural circuit formation. The survival rate of premature infants has increased significantly in recent years. The large morphological differences of the preterm brain at 33 or 36 postmenstrual weeks (PMW) from the brain at 40PMW (full term) make it necessary to establish age-specific atlases for preterm brains. In this study, with high quality (1.5 × 1.5 × 1.6 mm3 imaging resolution) diffusion tensor imaging (DTI) data obtained from 84 healthy preterm and term-born neonates, we established age-specific preterm and term-born brain templates and atlases at 33, 36 and 39PMW. Age-specific DTI templates include a single-subject template, a population-averaged template with linear transformation and a population-averaged template with nonlinear transformation. Each of the age-specific DTI atlases includes comprehensive labeling of 126 major gray matter (GM) and white matter (WM) structures, specifically 52 cerebral cortical structures, 40 cerebral WM structures, 22 brainstem and cerebellar structures and 12 subcortical GM structures. From 33 to 39 PMW, dramatic morphological changes of delineated individual neural structures such as ganglionic eminence and uncinate fasciculus were revealed. The evaluation based on measurements of Dice ratio and L1 error suggested reliable and reproducible automated labels from the age-matched atlases compared to labels from manual delineation. Applying these atlases to automatically and effectively delineate microstructural changes of major WM tracts during the 3rd trimester was demonstrated. The established age-specific DTI templates and atlases of 33, 36 and 39 PMW brains may be used for not only understanding normal functional and structural maturational processes but also detecting biomarkers of neural disorders in the preterm brains.

Brain Oxygen Extraction by Using MRI in Older Individuals: Relationship to Apolipoprotein E Genotype and Amyloid Burden.

Background Apolipoprotein E4 (APOE4) is a major genetic risk factor for late-onset Alzheimer disease. However, the mechanisms by which APOE4 affects the brain, underpinning this risk, have not been fully elucidated. Purpose To investigate the influence of APOE4 on global cerebral oxygen extraction fraction (OEF) and possible mediation through amyloid burden by using MRI-based brain oxygen extraction technique. Materials and Methods Participants were enrolled from a longitudinal prospective study, the Biomarkers for Older Controls at Risk for Dementia study (data collected from January 2015 to December 2017), of whom 35% (50 of 143 participants) were APOE4 carriers. OEF was measured by using a T2-relaxation-under-spin-tagging MRI technique with a 3.0-T MRI system. PET acquired with carbon 11-labeled Pittsburgh compound B tracer was available in 119 participants to measure amyloid burden. Cognitive performance was assessed by using domain-specific composite scores including executive function, episodic memory, visual-spatial processing, and language. Linear regression analysis was performed to investigate the relationship between APOE4, OEF, and amyloid burden. The association between OEF and cognitive function was studied for the entire study cohort and separately for the APOE4 carriers and noncarriers. Results A total of 143 cognitively healthy individuals (mean age 6 standard deviation, 69.1 years 6 8.2; 57 men and 86 women) were studied. APOE4 genetic status was associated with lower OEF (noncarriers, 41.1% 6 5.8; one E4 allele, 40.1% 6 4.9; two E4 alleles, 36.7% 6 4.5; P = .03). Furthermore, among APOE4 carriers, lower OEF correlated with lower executive function scores (b = 0.079 z score for each percent change in OEF; P = .03). Amyloid burden and OEF were independently associated with APOE4 but were not associated with one another, suggesting that the effect of APOE4 on OEF is not mediated by amyloid. Conclusion MRI-based brain oxygen extraction shows that cognitively healthy carriers of the apolipoprotein E4 gene manifest diminished brain oxygen extraction capacity independent of amyloid burden. ©RSNA, 2019 Online supplemental material is available for this article.

Impaired Recognition of Emotional Faces after Stroke Involving Right Amygdala or Insula.

Despite its basic and translational importance, the neural circuitry supporting the perception of emotional faces remains incompletely understood. Functional imaging studies and chronic lesion studies indicate distinct roles of the amygdala and insula in recognition of fear and disgust in facial expressions, whereas intracranial encephalography studies, which are not encumbered by variations in human anatomy, indicate a somewhat different role of these structures. In this article, we leveraged lesion-mapping techniques in individuals with acute right hemisphere stroke to investigate lesions associated with impaired recognition of prototypic emotional faces before significant neural reorganization can occur during recovery from stroke. Right hemisphere stroke patients were significantly less accurate than controls on a test of emotional facial recognition for both positive and negative emotions. Patients with right amygdala or anterior insula lesions had significantly lower scores than other right hemisphere stroke patients on recognition of angry and happy faces. Lesion volume within several regions, including the right amygdala and anterior insula, each independently contributed to the error rate in recognition of individual emotions. Results provide additional support for a necessary role of the right amygdala and anterior insula within a network of regions underlying recognition of facial expressions, particularly those that have biological importance or motivational relevance and have implications for clinical practice.

Mapping the critical gestational age at birth that alters brain development in preterm-born infants using multi-modal MRI.

Preterm birth adversely affects postnatal brain development. In order to investigate the critical gestational age at birth (GAB) that alters the developmental trajectory of gray and white matter structures in the brain, we investigated diffusion tensor and quantitative T2 mapping data in 43 term-born and 43 preterm-born infants. A novel multivariate linear model-the change point model, was applied to detect change points in fractional anisotropy, mean diffusivity, and T2 relaxation time. Change points captured the "critical" GAB value associated with a change in the linear relation between GAB and MRI measures. The analysis was performed in 126 regions across the whole brain using an atlas-based image quantification approach to investigate the spatial pattern of the critical GAB. Our results demonstrate that the critical GABs are region- and modality-specific, generally following a central-to-peripheral and bottom-to-top order of structural development. This study may offer unique insights into the postnatal neurological development associated with differential degrees of preterm birth.

Stroke of bad luck?

We hypothesized that distinct acute right hemisphere lesions disrupt separate components of valuation and emotional response to winning and losing money and of emotional empathy in observing a partner win or lose money. We measured skin conductance response (SCR) and ratings of emotions when acute right hemisphere stroke patients or healthy controls won or lost money in roulette, or when they watched a partner win or lose. Our results showed that percentage of damage after stroke to right anterior insula and frontal operculum negatively correlated with both SCR to winning and losing and difference between rating wins versus losses.

Picturing the Size and Site of Stroke With an Expanded National Institutes of Health Stroke Scale.

BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) includes minimal assessment of cognitive function, particularly in right hemisphere (RH) stroke. Descriptions of the Cookie Theft picture from the NIHSS allow analyses that (1) correlate with aphasia severity and (2) identify communication deficits in RH stroke. We hypothesized that analysis of the picture description contributes valuable information about volume and location of acute stroke. METHODS: We evaluated 67 patients with acute ischemic stroke (34 left hemisphere [LH]; 33 RH) with the NIHSS, analysis of the Cookie Theft picture, and magnetic resonance imaging, compared with 35 sex- and age-matched controls. We evaluated descriptions for total content units (CU), syllables, ratio of left:right CU, CU/minute, and percent interpretive CU, based on previous studies. Lesion volume and percent damage to regions of interest were measured on diffusion-weighted imaging. Multivariable linear regression identified variables associated with infarct volume, independently of NIHSS score, age and sex. RESULTS: Patients with RH and LH stroke differed from controls, but not from each other, on CU, syllables/CU, and CU/minute. Left:right CU was lower in RH compared with LH stroke. CU, syllables/CU, and NIHSS each correlated with lesion volume in LH and RH stroke. Lesion volume was best accounted by a model that included CU, syllables/CU, NIHSS, left:right CU, percent interpretive CU, and age, in LH and RH stroke. Each discourse variable and NIHSS score were associated with percent damage to different regions of interest, independently of lesion volume and age. CONCLUSIONS: Brief picture description analysis complements NIHSS scores in predicting stroke volume and location.

Probabilistic maps of the white matter tracts with known associated functions on the neonatal brain atlas: Application to evaluate longitudinal developmental trajectories in term-born and preterm-born infants.

Diffusion tensor imaging (DTI) has been widely used to investigate the development of the neonatal and infant brain, and deviations related to various diseases or medical conditions like preterm birth. In this study, we created a probabilistic map of fiber pathways with known associated functions, on a published neonatal multimodal atlas. The pathways-of-interest include the superficial white matter (SWM) fibers just beneath the specific cytoarchitectonically defined cortical areas, which were difficult to evaluate with existing DTI analysis methods. The Jülich cytoarchitectonic atlas was applied to define cortical areas related to specific brain functions, and the Dynamic Programming (DP) method was applied to delineate the white matter pathways traversing through the SWM. Probabilistic maps were created for pathways related to motor, somatosensory, auditory, visual, and limbic functions, as well as major white matter tracts, such as the corpus callosum, the inferior fronto-occipital fasciculus, and the middle cerebellar peduncle, by delineating these structures in eleven healthy term-born neonates. In order to characterize maturation-related changes in diffusivity measures of these pathways, the probabilistic maps were then applied to DTIs of 49 healthy infants who were longitudinally scanned at three time-points, approximately five weeks apart. First, we investigated the normal developmental pattern based on 19 term-born infants. Next, we analyzed 30 preterm-born infants to identify developmental patterns related to preterm birth. Last, we investigated the difference in diffusion measures between these groups to evaluate the effects of preterm birth on the development of these functional pathways. Term-born and preterm-born infants both demonstrated a time-dependent decrease in diffusivity, indicating postnatal maturation in these pathways, with laterality seen in the corticospinal tract and the optic radiation. The comparison between term- and preterm-born infants indicated higher diffusivity in the preterm-born infants than in the term-born infants in three of these pathways: the body of the corpus callosum; the left inferior longitudinal fasciculus; and the pathway connecting the left primary/secondary visual cortices and the motion-sensitive area in the occipitotemporal visual cortex (V5/MT+). Probabilistic maps provided an opportunity to investigate developmental changes of each white matter pathway. Whether alterations in white matter pathways can predict functional outcomes will be further investigated in a follow-up study.

Critical role of the right uncinate fasciculus in emotional empathy.

OBJECTIVE: Common neurological diseases or injuries that can affect the right hemisphere, including stroke, traumatic brain injury, and frontotemporal dementia, disrupt emotional empathy-the ability to share in and make inferences about how other people feel. This impairment negatively impacts social interactions and relationships. Accumulating evidence indicates that emotional empathy depends on coordinated functions of orbitofrontal cortex, anterior insula, anterior cingulate, temporal pole, and amygdala, but few studies have investigated effects of lesions to white matter tracts that connect these structures. We tested the hypothesis that percentage damage to specific white matter tracts connecting these gray matter structures predicts error rate in an emotional empathy task after acute right hemisphere ischemic stroke. METHODS: We used multivariate linear regression with percentage damage to 8 white matter tracts, age, and education as independent variables and error rate on emotional empathy as the dependent variable to test a predictive model of emotional empathy in 30 patients with acute ischemic right hemisphere stroke. RESULTS: Percentage damage to 8 white matter tracts along with age and education predicted the error rate in emotional empathy, but only percentage damage to the uncinate fasciculus was independently associated with error rate. Participants with right uncinate fasciculus lesions were significantly more impaired than right hemisphere stroke patients without uncinate fasciculus lesions in the emotional empathy task. INTERPRETATION: The right uncinate fasciculus plays an important role in the emotional empathy network. Patients with lesions in this network should be evaluated for empathy, so that deficits can be addressed.