Brain Surface Research Articles

A robust motion correction technique for infrared thermography during awake craniotomy

PurposeIntraoperative infrared thermography is an emerging technique for image-guided neurosurgery, whereby physiological and pathological processes result in temperature changes over space and time. However, motion during data collection leads to downstream artifacts in thermography analyses. We develop a fast, robust technique for motion estimation and correction as a preprocessing step for brain surface thermography recordings.MethodsA motion correction technique for thermography was developed which approximates the deformation field associated with motion as a grid of two-dimensional bilinear splines (Bispline registration), and a regularization function was designed to constrain motion to biomechanically feasible solutions. The performance of the proposed Bispline registration technique was compared to phase correlation, a band-stop filter, demons registration, and the Horn–Schunck and Lucas–Kanade optical flow techniques.ResultsAll methods were analyzed using thermography data from ten patients undergoing awake craniotomy for brain tumor resection, and performance was compared using image quality metrics. The proposed method had the lowest mean-squared error and the highest peak-signal-to-noise ratio of all methods tested and performed slightly worse than phase correlation and Demons registration on the structural similarity index metric (p < 0.01, Wilcoxon signed-rank test). Band-stop filtering and the Lucas–Kanade method were not strong attenuators of motion, while the Horn–Schunck method was well-performing initially but weakened over time.ConclusionBispline registration had the most consistently strong performance out of all the techniques tested. It is relatively fast for a nonrigid motion correction technique, capable of processing ten frames per second, and could be a viable option for real-time use. Constraining the deformation cost function through regularization and interpolation appears sufficient for fast, monomodal motion correction of thermal data during awake craniotomy.

Using virtual lines of navigation for a successful transcortical approach.

Neuronavigation systems have become essential tools in image-guided neurosurgery that aid in the accurate resection of brain tumors. Recent advancements to these devices can indicate the precise location of lesions but can also project an augmented reality (AR) image on the microscope eyepiece to facilitate a successful surgical operation. Although the transcortical approach is a very popular method in neurosurgery, it can lead to disorientation and can cause unnecessary brain damage when the distance from the brain surface to the lesion is long. Herein, we report on an actual case in which a virtual line from AR images was used to assist the transcortical approach. A virtual line connecting the entry point and the target point, which were set as the navigation route, was created using Stealth station S7® (Medtronic, Minneapolis, USA). This line was projected as an AR image on the microscope eyepiece. It was possible to reach the target point by proceeding through the white matter along the displayed virtual line. The lesion was reached within a short duration using virtual line without disorientation. Setting a virtual line as an AR image using neuronavigation is a simple and accurate method that can effectively support the conventional transcortical approach.

A novel micro-ECoG recording method for recording multisensory neural activity from the parietal to temporal cortices in mice

Characterization of inter-regional interactions in brain is essential for understanding the mechanism relevant to normal brain function and neurological disease. The recently developed flexible micro (μ)-electrocorticography (μECoG) device is one prominent method used to examine large-scale cortical activity across multiple regions. The sheet-shaped μECoG electrodes arrays can be placed on a relatively wide area of cortical surface beneath the skull by inserting the device into the space between skull and brain. Although rats and mice are useful tools for neuroscience, current μECoG recording methods in these animals are limited to the parietal region of cerebral cortex. Recording cortical activity from the temporal region of cortex in mice has proven difficult because of surgical barriers created by the skull and surrounding temporalis muscle anatomy. Here, we developed a sheet-shaped 64-channel μECoG device that allows access to the mouse temporal cortex, and we determined the factor determining the appropriate bending stiffness for the μECoG electrode array. We also established a surgical technique to implant the electrode arrays into the epidural space over a wide area of cerebral cortex covering from the barrel field to olfactory (piriform) cortex, which is the deepest region of the cerebral cortex. Using histology and computed tomography (CT) images, we confirmed that the tip of the μECoG device reached to the most ventral part of cerebral cortex without causing noticeable damage to the brain surface. Moreover, the device simultaneously recorded somatosensory and odor stimulus-evoked neural activity from dorsal and ventral parts of cerebral cortex in awake and anesthetized mice. These data indicate that our μECoG device and surgical techniques enable the recording of large-scale cortical activity from the parietal to temporal cortex in mice, including somatosensory and olfactory cortices. This system will provide more opportunities for the investigation of physiological functions from wider areas of the mouse cerebral cortex than those currently available with existing ECoG techniques.

Downstream signalling of the disease-associated mutations on GPR56/ADGRG1.

GPR56/ADGRG1 is an adhesion G protein-coupled receptor (GPCR) and mutations on this receptor cause cortical malformation due to the over-migration of neural progenitor cells on brain surface. At pial surface, GPR56 interacts with collagen III, induces Rho-dependent activation through Gα12/13 and inhibits the neuronal migration. In human glioma cells, GPR56 inhibits cell migration through Gαq/11 -dependent Rho pathway. GPR56-tetraspanin complex is known to couple Gαq/11 . GPR56 is an aGPCR that couples with various G proteins and signals through different downstream pathways. In this study, bilateral frontoparietal polymicrogyria (BFPP) mutants disrupting GPR56 function but remaining to be expressed on plasma membrane were used to study receptor signalling through Gα12 , Gα13 and Gα11 with BRET biosensors. GPR56 showed coupling with all three G proteins and activated heterotrimeric G protein signalling upon stimulation with Stachel peptide. However, BFPP mutants showed different signalling defects for each G protein indicative of distinct activation and signalling properties of GPR56 for Gα12 , Gα13 or Gα11 . β-arrestin recruitment was also investigated following the activation of GPR56 with Stachel peptide using BRET biosensors. N-terminally truncated GPR56 showed enhanced β-arrestin recruitment; however, neither wild-type receptor nor BFPP mutants gave any measurable recruitment upon Stachel stimulation, pointing different activation mechanisms for β-arrestin involvement.

Alteration of surface morphology and core features in adolescents with borderline personality disorder

BackgroundAccurate early diagnosis of adolescent borderline personality disorder (BPD) is critical for prompt treatment. The aim of this study was to assess the alteration of brain surface morphology and to evaluate its relationship with core features in adolescent BPD. MethodsA total of 52 adolescents with BPD aged 12–17 years and 39 age- and sex-matched healthy controls (HCs) were prospectively enrolled into the study. Brain magnetic resonance imaging (MRI) was obtained with both 3D-T1 weighted structural sequence and resting-state functional data. The structural data was analyzed for surface morphology parameters including the local gyrification index (LGI), mean curvature and surface area. The functional MRI data was analyzed for seed-based functional connectivity (FC). Correlative analysis of surface morphology and core features of adolescent BPD was performed. ResultsAdolescents with BPD showed the following altered surface morphology in the limbic-cortical circuit when compared to the HCs: (1) reduced LGI in the left fusiform and right superior temporal gyrus; (2) reduced mean curvature in the left precentral gyrus and right rostral anterior cingulate cortex, and increased mean curvature in the bilateral pericalcarine; and (3) reduced surface area in the left paracentral gyrus, left pars triangularis, right insula and right lateral orbitofrontal gyrus (P < 0.05, FWE correction). In addition, these brain regions with altered surface morphology were significantly correlated with several core features including the mood instability, self-identity problems, and non-suicidal self-injury behavior in adolescents with BPD (P < 0.05). Furthermore, there was enhanced functional connectivity among these altered brain regions within the limbic-cortical circuit (voxel P < 0.001, cluster P < 0.05, FWE corrected). ConclusionsAdolescents with BPD had significant alterations of brain surface morphology in the limbic-cortical circuit, which was correlated with core BPD features. These results implicated the surface morphology parameters and FC alterations may potentially serve as neuroimaging biomarkers for adolescents with BPD.

Hypoxic microenvironment as a crucial factor triggering events leading to rupture of intracranial aneurysm

Subarachnoid hemorrhage being the rupture of intracranial aneurysm (IA) as a major cause has quite poor prognosis, despite the modern technical advances. Thereby, the mechanisms underlying the rupture of lesions should be clarified. Recently, we and others have clarified the formation of vasa vasorum in IA lesions presumably for inflammatory cells to infiltrate in lesions as the potential histopathological alternation leading to rupture. In the present study, we clarified the origin of vasa vasorum as arteries located at the brain surface using 3D-immunohistochemistry with tissue transparency. Using Hypoxyprobe, we then found the presence of hypoxic microenvironment mainly at the adventitia of intracranial arteries where IA is formed. In addition, the production of vascular endothelial growth factor (VEGF) from cultured macrophages in such a hypoxic condition was identified. Furthermore, we found the accumulation of VEGF both in rupture-prone IA lesions induced in a rat model and human unruptured IA lesions. Finally, the VEGF-dependent induction of neovessels from arteries on brain surface was confirmed. The findings from the present study have revealed the potential role of hypoxic microenvironment and hypoxia-induced VEGF production as a machinery triggering rupture of IAs via providing root for inflammatory cells in lesions to exacerbate inflammation.

Complement activation and increased anaphylatoxin receptor expression are associated with cortical grey matter lesions and the compartmentalised inflammatory response of multiple sclerosis.

The extent of cortical pathology is an important determinant of multiple sclerosis (MS) severity. Cortical demyelination and neurodegeneration are related to inflammation of the overlying leptomeninges, a more inflammatory CSF milieu and with parenchymal microglia and astroglia activation. These are all components of the compartmentalised inflammatory response. Compartmentalised inflammation is a feature of progressive MS, which is not targeted by disease modifying therapies. Complement is differentially expressed in the MS CSF and complement, and complement receptors, are associated with demyelination and neurodegeneration. To better understand if complement activation in the leptomeninges is associated with underlying cortical demyelination, inflammation, and microglial activation, we performed a neuropathological study of progressive MS (n = 22, 14 females), neuroinflammatory (n = 8), and non-neurological disease controls (n = 10). We then quantified the relative extent of demyelination, connective tissue inflammation, complement, and complement receptor positive microglia/macrophages. Complement was elevated at the leptomeninges, subpial, and within and around vessels of the cortical grey matter. The extent of complement C1q immunoreactivity correlated with connective tissue infiltrates, whilst activation products C4d, Bb, and C3b associated with grey matter demyelination, and C3a receptor 1+ and C5a receptor 1+ microglia/macrophages closely apposed C3b labelled cells. The density of C3a receptor 1+ and C5a receptor 1+ cells was increased at the expanding edge of subpial and leukocortical lesions. C5a receptor 1+ cells expressed TNFα, iNOS and contained puncta immunoreactive for proteolipid protein, neurofilament and synaptophysin, suggesting their involvement in grey matter lesion expansion. The presence of products of complement activation at the brain surfaces, their association with the extent of underlying pathology and increased complement anaphylatoxin receptor positive microglia/macrophages at expanding cortical grey matter lesions, could represent a target to modify compartmentalised inflammation and cortical demyelination.

Comparison Between the Supracerebellar Infratentorial and Precuneal Interhemispheric, Transtentorial Approaches to the Cerebellomesencephalic Fissure: An Anatomoradiological Study and Illustrative Cases.

The dorsal brainstem and cerebellomesencephalic fissure are challenging surgical targets. To afford a preferentially craniocaudal trajectory to this region, the precuneal interhemispheric transtentorial approach (PCIT) has been proposed. To didactically describe and compare exposures and anatomic indications of the supracerebellar infratentorial approach (SCIT) and PCIT to the cerebellomesencephalic fissure. Nine formalin-fixed, latex-injected cadaveric head specimens were used to perform a midline SCIT and bilateral PCITs and measure the distance of each approach. Twenty-four formalin-fixed specimens were used to measure the distance from the most posterior cortical bridging vein entering the superior sagittal sinus to the calcarine sulcus and the torcula. Fifty-one magnetic resonance images were reviewed to calculate the angle of each approach. Three illustrative surgical cases were described. Mean distances from the brain or cerebellar surface to the operative target of the PCIT and SCIT were 7.1 cm (range: 5-7.7 cm) and 5.5 cm (range: 3.8-6.2 cm), respectively. The SCIT provided direct access to structures of the quadrigeminal cistern bilaterally. The PCIT provided access from the ipsilateral inferior colliculus to the ipsilateral infratrochlear zone. The PCIT's benefit was the direct access it provided to the cerebellomesencephalic fissure because of its superior to inferior trajectory. The PCIT is indicated for unilateral lesions of the cerebellomesencephalic fissure and dorsal brainstem that harbor a craniocaudal long axis and do not have a superior extension beyond the superior colliculi. The SCIT is beneficial for lesions that extend bilaterally, have an anteroposterior long axis, or involve the Galenic complex.

Evans Blue and Fluorescein Isothiocyanate-Dextran Double Labeling Reveals Precise Sequence of Vascular Leakage and Glial Responses after Exposure to Mild-Level Blast-Associated Shock Waves.

Abstract Blast-induced shock waves (BSWs) are responsible for several aspects of psychiatric disorders that are collectively termed mild traumatic brain injury (mTBI). The pathophysiology of mTBI includes vascular leakage resulting from blood-brain barrier (BBB) disruption. In this study, the precise sequence of BBB breakdown was examined using an Evans blue and fluorescein isothiocyanate (FITC)-dextran double labeling technique. Evans blue solution was injected into the tail vein of male C57BL6/J mice just before and 4 h, 1 day, 3 days, and 7 days after a single BSW exposure at as low as 25-kPa peak overpressure. In contrast, the FITC-dextran solution was transcardially injected just before perfusion fixation. Differences in the labeling time-point revealed that BBB breakdown was initiated after approximately 3 h, with significant remodeling by 1 day, and continued until 7 days after BSW exposure. BBB breakdown was upregulated in three distinct regions, namely the brain surface and subsurface areas facing the skull, regions closely associated with capillaries, and the circumventricular organ and choroid plexus. These regions showed distinct responses to BSW; moreover, clusters of reactive astrocytes were closely associated with the sites of BBB breakdown. In severe cases, these reactive astrocytes recruited activated microglia. Our findings provide important insights into the pathogenesis underlying mTBI and indicate that even mild BSW exposure affects the whole brain.

Sex differences of brain cortical structure in major depressive disorder.

Major depressive disorder (MDD) has different clinical presentations in males and females. However, the neuroanatomical mechanisms underlying these sex differences are not fully understood. The purpose of present study was to explore the sex differences in brain cortical thickness (CT) and surface area (SA) of MDD and the relationship between these differences and clinical manifestations in different gender. High-resolution T1-weighted images were acquired from 61 patients with MDD and 61 healthy controls (36 females and 25 males, both). The sex differences in CT and SA were obtained using the FreeSurfer software and compared between every two groups by post hoc test. Spearman correlation analysis was also performed to explore the relationships between these regions and clinical characteristics. In male patients with MDD, the CT of the right precentral was thinner compared to female patients, although this did not survive Bonferroni correction. The SA of several regions, including right superior frontal, medial orbitofrontal gyrus, inferior frontal gyrus triangle, superior temporal, middle temporal, lateral occipital gyrus, and inferior parietal lobule in female patients with MDD was smaller than that in male patients (P<0.01 after Bonferroni correction). In female patients, the SA of the right superior temporal (r=0.438, P=0.008), middle temporal (r=0.340, P=0.043), and lateral occipital gyrus (r=0.372, P=0.025) were positively correlated with illness duration. The current study provides evidence of sex differences in CT and SA in patients with MDD, which may improve our understanding of the sex-specific neuroanatomical changes in the development of MDD.

Functional imaging and anatomical connections in squirrel monkeys reveal parietal-frontal circuits underlying eye movements.

The posterior parietal cortex (PPC) of squirrel monkeys contains subregions where long trains of intracortical microstimulation evoke complex, behaviorally meaningful movements. Recently, we showed that such stimulation of a part of the PPC in the caudal lateral sulcus (LS) elicits eye movements in these monkeys. Here, we studied the functional and anatomical connections of this oculomotor region we call parietal eye field (PEF) with frontal eye field (FEF) and other cortical regions in 2 squirrel monkeys. We demonstrated these connections with intrinsic optical imaging and injections of anatomical tracers. Optical imaging of frontal cortex during stimulation of the PEF evoked focal functional activation within FEF. Tracing studies confirmed the functional PEF-FEF connections. Moreover, tracer injections revealed PEF connections with other PPC regions on the dorsolateral and medial brain surface, cortex in the caudal LS, and visual and auditory cortical association areas. Subcortical projections of PEF were primarily with superior colliculus, and pontine nuclei as well as nuclei of the dorsal posterior thalamus and caudate. These findings suggest that PEF in squirrel monkey is homologous to lateral intraparietal (LIP) area of macaque, supporting the notion that these brain circuits are organized similarly to mediate ethologically relevant oculomotor behaviors.

In Vivo Deep-Brain 3- and 4-Photon Fluorescence Imaging of Subcortical Structures Labeled by Quantum Dots Excited at the 2200 nm Window.

Multiphoton microscopy (MPM) is an enabling technology for visualizing deep-brain structures at high spatial resolution in vivo. Within the low tissue absorption window, shifting to longer excitation wavelengths reduces tissue scattering and boosts penetration depth. Recently, the 2200 nm excitation window has emerged as the last and longest window suitable for deep-brain MPM. However, multiphoton fluorescence imaging at this window has not been demonstrated, due to the lack of characterization of multiphoton properties of fluorescent labels. Here we demonstrate technologies for measuring both the multiphoton excitation and emission properties of fluorescent labels at the 2200 nm window, using (1) 3-photon (ησ3) and 4-photon action cross sections (ησ4) and (2) 3-photon and 4-photon emission spectra both ex vivo and in vivo of quantum dots. Our results show that quantum dots have exceptionally large ησ3 and ησ4 for efficient generation of multiphoton fluorescence. Besides, the 3-photon and 4-photon emission spectra of quantum dots are essentially identical to those of one-photon emission, which change negligibly subject to the local environment of circulating blood. Based on these characterization results, we further demonstrate deep-brain vasculature imaging in vivo. Due to the superb multiphoton properties of quantum dots, 3-photon and 4-photon fluorescence imaging reaches a maximum brain imaging depth of 1060 and 940 μm below the surface of a mouse brain, respectively, which enables the imaging of subcortical structures. We thus fill the last gap in multiphoton fluorescence imaging in terms of wavelength selection.

Brain Structure Relations With Psychopathology Trajectories in the ABCD Study

A general psychopathology (p) factor captures shared variation across mental disorders. Structural neural alterations have been associated with the p factor concurrently, but less is known about whether these alterations relate to within-person change in the p factor over time, especially during preadolescence, a period of neurodevelopmental changes. This study examined whether baseline brain structure was prospectively related to the trajectory of the p factor and specific forms of psychopathology over 2 years in 9,220 preadolescents (aged 9-10 at baseline) from the Adolescent Brain Cognitive Development Study (ABCD). Longitudinal multilevel models were conducted to determine whether baseline brain structure (volume, surface area, thickness) was associated with between-person differences and within-person change in the p factor (from a higher-order confirmatory factor model) and internalizing, externalizing, neurodevelopmental, somatization, and detachment factor scores (from a correlated factors model) over 3 study waves. Smaller global volume and surface area, but not thickness, were associated with higher between-person levels of the p factor scores, which persisted over time. None of the brain structure measures were related to within-person change in the p factor scores. Lower baseline cortical thickness was associated with steeper decreases in internalizing psychopathology, which was driven by lower thickness within sensorimotor and temporal regions. These novel results identify specific brain structure features that might contribute to transdiagnostic psychopathology development in preadolescence. Children with smaller total brain volume and surface area may be vulnerable to persistent general psychopathology during preadolescence. Cortical thinning reflective of pruning and myelination in sensorimotor and temporal brain regions specifically may protect against increases in internalizing, but not general psychopathology, during preadolescence.

Restricted language access during childhood affects adult brain structure in selective language regions

Due to the ubiquitous nature of language in the environment of infants, how it affects the anatomical structure of the brain language system over the lifespan is not well understood. In this study, we investigated the effects of early language experience on the adult brain by examining anatomical features of individuals born deaf with typical or restricted language experience in early childhood. Twenty-two deaf adults whose primary language was American Sign Language and were first immersed in it at ages ranging from birth to 14 y participated. The control group was 21 hearing non-signers. We acquired T1-weighted magnetic resonanceimages and used FreeSurfer [B. Fischl,Neuroimage 62, 774-781(2012)]to reconstruct the brain surface. Using an a priori regions of interest (ROI) approach, we identified 17 language and 19 somatomotor ROIs in each hemisphere from the Human Connectome Project parcellation map [M. F. Glasseretal.,Nature 536, 171-178 (2016)]. Restricted language experience in early childhood was associated with negative changes in adjusted grey matter volume and/or cortical thickness in bilateral fronto-temporal regions. No evidence of anatomical differences was observed in any of these regions when deaf signers with infant sign language experience were compared with hearing speakers with infant spoken language experience, showing that the effects of early language experience on the brain language system are supramodal.

Age- and sex-related differences in cortical morphology and their relationships with cognitive performance in healthy middle-aged and older adults.

The impacts of age and sex on brain structures related to cognitive function may be important for understanding the role of aging in Alzheimer disease for both sexes. We intended to investigate the age and sex differences of cortical morphology in middle-aged and older adults and their relationships with the decline of cognitive function. In this cross-sectional study, we examined the cortical morphology in 204 healthy middle-aged and older adult participants aged 45 to 89 years using structural magnetic resonance imaging (sMRI) data from the Dallas Lifespan Brain Study data set. Brain cortical thickness, surface complexity, and gyrification index were analyzed through a completely automated surface-based morphometric analysis using the CAT12 toolbox. Furthermore, we explored the correlation between cortical morphology differences and test scores for processing speed and working memory. There were no significant interactions of age and sex with cortical thickness, fractal dimension, or gyrification index. Rather, we found that both males and females showed age-related decreases in cortical thickness, fractal dimension, and gyrification index. There were significant sex differences in the fractal dimension in middle-aged participants and the gyrification index in older adult participants. In addition, there were significant positive correlations between the cortical thickness of the right superior frontal gyrus and Wechsler Adult Intelligence Scale (WAIS)-III Letter-Number Sequencing test scores in males (r=0.394; P<0.001; 95% CI for r values 0.216-0.577) and females (r=0.344; P<0.001; 95% CI for r values 0.197-0.491), respectively. Furthermore, a significant relationship between the gyrification index of the right supramarginal gyrus (SupraMG) and WAIS-III Digit Symbol test scores was observed in older adult participants (r=0.375; P<0.001; 95% CI for r values 0.203-0.522). The results suggest that, compared with males, females have more extensive differences in cortical morphology. The gyrification index of the right SupraMG can be used as an imaging marker of sexual cognitive differences between males and females in older adults. This study helps to further understand sex differences in the aging of the brain and cognition.

Abstract WP221: Rnaseq Reveals An Angiogenic Signature Of Leptomeningeal Collaterals In Pig Brain.

Introduction: The leptomeningeal collaterals (LMCs) are specialized brain surface arterioles that interconnect the distalmost arterioles (DMAs) of the major cerebral arteries. In normal conditions, flow in LMCs is negligible. However, during ischemic stroke, the LMCs provide a vital route for rescue blood flow from neighboring vessel territories, thereby lessening ischemic injury and improving outcome. With sustained flow, the LMCs rapidly remodel to further increase perfusion capacity. The LMCs differ in function and molecular composition compared to DMAs, however, a comprehensive transcriptional signature of these two vessel types is not available. Therefore, we developed methods to identify and isolate LMCs and DMAs from pig brain for subsequent unbiased RNAseq analysis. Methods: Duroc pigs were used to due to their larger vascular anatomy and gyrencephalic brains. We first mapped the cerebral vasculature and location of LMCs using blue dye infusion (surface vessel tracing) and BaSO4 microparticle infusion (3D microCT imaging). Having established location of LMCs, we infused an RNAlater/blue ink solution to facilitate vessel visualization and RNA stabilization during dissection. Harvested LMCs and DMAs were pooled by type and processed for RNAseq and analysis by R. Results: RNAseq analysis of LMCs and DMAs revealed 349 differentially expressed genes (DEGs) (adjusted p value &lt; 0.05, fold change &gt; 0.5), of which 241 were upregulated and 108 were down regulated in LMCs. Gene ontology (GO) analysis showed upregulation of biological processes including “vasculature development”, “sprouting angiogenesis”, “angiogenesis”, and “regulation of smooth muscle cell proliferation” in the LMC group. Angiogenesis related genes ( Cldn5 , Kdr , Vegfc , and Vwf ) were markedly upregulated in LMCs compared to DMAs (1.75 to 2.75 fold). In contrast, “extracellular matrix organization” and “positive regulation of smooth muscle cell migration” were among the most downregulated biological processes in LMCs. Conclusions: Our unbiased RNAseq approach revealed numerous DEGs between LMCs and DMAs. Interestingly, GO analysis revealed a proangiogenic signature in LMCs, which may shed new light on how they are able to rapidly remodel following ischemic stroke.

A Unique "Reversed" Migration of Neurons in the Developing Claustrum.

The claustrum (CLA) is a cluster of neurons located between the insular cortex and striatum. Many studies have shown that the CLA plays an important role in higher brain function. Additionally, growing evidence suggests that CLA dysfunction is associated with neuropsychological symptoms. However, how the CLA is formed during development is not fully understood. In the present study, we analyzed the development of the CLA, especially focusing on the migration profiles of CLA neurons in mice of both sexes. First, we showed that CLA neurons were generated between embryonic day (E) 10.5 and E12.5, but mostly at E11.5. Next, we labeled CLA neurons born at E11.5 using the FlashTag technology and revealed that most neurons reached the brain surface by E13.5 but were distributed deep in the CLA 1 d later at E14.5. Time-lapse imaging of GFP-labeled cells revealed that some CLA neurons first migrated radially outward and then changed their direction inward after reaching the surface. Moreover, we demonstrated that Reelin signal is necessary for the appropriate distribution of CLA neurons. The switch from outward to "reversed" migration of developing CLA neurons is distinct from other migration modes, in which neurons typically migrate in a certain direction, which is simply outward or inward. Future elucidation of the characteristics and precise molecular mechanisms of CLA development may provide insights into the unique cognitive functions of the CLA.SIGNIFICANCE STATEMENT The claustrum (CLA) plays an important role in higher brain function, and its dysfunction is associated with neuropsychological symptoms. Although psychiatric disorders are increasingly being understood as disorders of neurodevelopment, little is known about CLA development, including its neuronal migration profiles and underlying molecular mechanisms. Here, we investigated the migration profiles of CLA neurons during development and found that they migrated radially outward and then inward after reaching the surface. This switch in the migratory direction from outward to inward may be one of the brain's fundamental mechanisms of nuclear formation. Our findings enable us to investigate the relationship between CLA maldevelopment and dysfunction, which may facilitate understanding of the pathogenesis of some psychiatric disorders.

Structural and Functional Brain Changes in Acute Takotsubo Syndrome

BackgroundTakotsubo syndrome mimics an acute myocardial infarction, typically in the aftermath of mental or physical stress. ObjectivesThe mechanism by which emotional processing in the context of stress leads to significant cardiac injury is poorly understood, so a full exploration of brain structure and function in takotsubo syndrome patients merits investigation. MethodsTwenty-five acute (<5 days) takotsubo patients and 25 control subjects were recruited into this observational cross-sectional study. Surface-based morphometry was carried out on magnetic resonance imaging (MRI) brain scans to extract cortical morphology based on volume, thickness, and surface area with the use of Freesurfer. Cortical morphology general linear models were corrected for age, sex, photoperiod, and total brain volume. Resting-state functional MRI and diffusion tensor tractography images were preprocessed and analyzed with the use of the Functional Magnetic Resonance Imaging of the Brain Diffusion Toolbox and Functional Connectivity Toolbox. ResultsThere was significantly smaller total white matter and subcortical gray matter volumes in takotsubo (P < 0.001), with smaller total brain surface area but increased total cortical thickness (both P < 0.001). Individual gray matter regions (hippocampus and others) were significantly smaller in takotsubo (P < 0.001); only thalamus and insula were larger (P < 0.001). There was significant hyperfunctional and hypofunctional connectivity in multiple areas, including thalamus-amygdala-insula and basal ganglia (P < 0.05). All structural tractography connections were increased in takotsubo (P < 0.05). ConclusionsThe authors showed smaller gray and white matter volumes driven by smaller cortical surface area, but increased cortical thickness and structural tractography connections with bidirectional changes in functional connectivity linked to emotion, language, reasoning, perception, and autonomic control. These are interventional targets in takotsubo patients’ rehabilitation.

Ear-EEG sensitivity modeling for neural sources and ocular artifacts.

The ear-EEG has emerged as a promising candidate for real-world wearable brain monitoring. While experimental studies have validated several applications of ear-EEG, the source-sensor relationship for neural sources from across the brain surface has not yet been established. In addition, modeling of the ear-EEG sensitivity to sources of artifacts is still missing. Through volume conductor modeling, the sensitivity of various configurations of ear-EEG is established for a range of neural sources, in addition to ocular artifact sources for the blink, vertical saccade, and horizontal saccade eye movements. Results conclusively support the introduction of ear-EEG into conventional EEG paradigms for monitoring neural activity that originates from within the temporal lobes, while also revealing the extent to which ear-EEG can be used for sources further away from these regions. The use of ear-EEG in scenarios prone to ocular artifacts is also supported, through the demonstration of proportional scaling of artifacts and neural signals in various configurations of ear-EEG. The results from this study can be used to support both existing and prospective experimental ear-EEG studies and applications in the context of sensitivity to both neural sources and ocular artifacts.

Region Expansion of Background Field Removal with Local Spherical Harmonics Approximation for Whole-brain Quantitative Susceptibility Mapping.

Quantitative susceptibility mapping (QSM) is useful for obtaining biological information. To calculate susceptibility distribution, it is necessary to calculate the local field caused by the differences of susceptibility between the tissues. The local field can be obtained by removing a background field from a total field acquired by MR phase image. Conventional approaches based on spherical mean value (SMV) filtering, which are widely used for background field calculations, fail to calculate the background field of the brain surface region corresponding to the radius of the SMV kernel, and consequently cannot calculate the QSM of the brain surface region. Accordingly, a new method calculating the local field by expansively removing the background field is proposed for whole brain QSM. The proposed method consists of two steps. First, the background field of the brain surface is calculated from the total field using a locally polynomial approximation of spherical harmonics. Second, the whole brain local field is calculated by SMV filtering with a constraint term of the background field of the brain surface. The parameters of the approximation were optimized to reduce calculation errors through simulations using both a numerical phantom and a measured human brain. Performance of the proposed method with the optimized parameters was quantitatively and visually compared with conventional methods in an experiment of five healthy volunteers. The proposed method showed the accurate local field over the expanded brain region in the simulation studies. It also showed consistent QSM with conventional methods inside of the brain surface and showed clear vein structures on the brain surface. The proposed method enables accurate calculation of whole brain QSM without eroding the brain surface region while maintaining same values inside of the brain surface as the conventional methods.