Distinct Nuclei Research Articles

Functional coupling of the orbitofrontal cortex and the basolateral amygdala mediates the association between spontaneous reappraisal and emotional response

Emotional regulation is known to be associated with activity in the amygdala. The amygdala is an emotion-generative region that comprises of structurally and functionally distinct nuclei. However, little is known about the contributions of different frontal-amygdala sub-region pathways to emotion regulation. Here, we investigated how functional couplings between frontal regions and amygdala sub-regions are involved in different spontaneous emotion regulation processes by using an individual-difference approach and a generalized psycho-physiological interaction (gPPI) approach. Specifically, 50 healthy participants reported their dispositional use of spontaneous cognitive reappraisal and expressive suppression in daily life and their actual use of these two strategies during the performance of an emotional-picture watching task. Results showed that functional coupling between the orbitofrontal cortex (OFC) and the basolateral amygdala (BLA) was associated with higher scores of both dispositional and actual uses of reappraisal. Similarly, functional coupling between the dorsolateral prefrontal cortex (dlPFC) and the centromedial amygdala (CMA) was associated with higher scores of both dispositional and actual uses of suppression. Mediation analyses indicated that functional coupling of the right OFC-BLA partially mediated the association between reappraisal and emotional response, irrespective of whether reappraisal was measured by dispositional use (indirect effect(SE)=-0.2021 (0.0811), 95%CI(BC)= [-0.3851, -0.0655]) or actual use (indirect effect(SE)=-0.1951 (0.0796), 95%CI(BC)= [-0.3654, -0.0518])). These findings suggest that spontaneous reappraisal and suppression involve distinct frontal- amygdala functional couplings, and the modulation of BLA activity from OFC may be necessary for changing emotional response during spontaneous reappraisal.

The Contribution of Thalamic Nuclei in Salience Processing.

The brain continuously receives diverse information about the external environment and changes in the homeostatic state. The attribution of salience determines which stimuli capture attention and, therefore, plays an essential role in regulating emotions and guiding behaviors. Although the thalamus is included in the salience network, the neural mechanism of how the thalamus contributes to salience processing remains elusive. In this mini-review, we will focus on recent advances in understanding the specific roles of distinct thalamic nuclei in salience processing. We will summarize the functional connections between thalamus nuclei and other key nodes in the salience network. We will highlight the convergence of neural circuits involved in reward and pain processing, arousal, and attention control in thalamic structures. We will discuss how thalamic activities represent salience information in associative learning and how thalamic neurons modulate adaptive behaviors. Lastly, we will review recent studies which investigate the contribution of thalamic dysfunction to aberrant salience processing in neuropsychiatric disorders, such as drug addiction, posttraumatic stress disorder (PTSD), and schizophrenia. Based on emerging evidence from both human and rodent research, we propose that the thalamus, different from previous studies that as an information relay, has a broader role in coordinating the cognitive process and regulating emotions.

Quail-chick grafting experiments corroborate that Tbr1-positive eminential prethalamic neurons migrate along three streams into hypothalamus, subpallium and septocommissural areas

The prethalamic eminence (PThE), a diencephalic caudal neighbor of the telencephalon and alar hypothalamus, is frequently described in mammals and birds as a transient embryonic structure, undetectable in the adult brain. Based on descriptive developmental analysis of Tbr1 gene brain expression in chick embryos, we previously reported that three migratory cellular streams exit the PThE rostralward, targeting multiple sites in the hypothalamus, subpallium and septocommissural area, where eminential cells form distinct nuclei or disperse populations. These conclusions needed experimental corroboration. In this work, we used the homotopic quail-chick chimeric grafting procedure at stages HH10/HH11 to demonstrate by fate-mapping the three predicted tangential migration streams. Some chimeric brains were processed for Tbr1 in situ hybridization, for correlation with our previous approach. Evidence supporting all three postulated migration streams is presented. The results suggested a slight heterochrony among the juxtapeduncular (first), the peripeduncular (next), and the eminentio-septal (last) streams, each of which followed differential routes. A possible effect of such heterochrony on the differential selection of medial to lateral habenular hodologic targets by the migrated neurons is discussed.

Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis.

Long-COVID is a postviral illness that can affect survivors of COVID-19, regardless of initial disease severity or age. Symptoms of long-COVID include fatigue, dyspnea, gastrointestinal and cardiac problems, cognitive impairments, myalgia, and others. While the possible causes of long-COVID include long-term tissue damage, viral persistence, and chronic inflammation, the review proposes, perhaps for the first time, that persistent brainstem dysfunction may also be involved. This hypothesis can be split into two parts. The first is the brainstem tropism and damage in COVID-19. As the brainstem has a relatively high expression of ACE2 receptor compared with other brain regions, SARS-CoV-2 may exhibit tropism therein. Evidence also exists that neuropilin-1, a co-receptor of SARS-CoV-2, may be expressed in the brainstem. Indeed, autopsy studies have found SARS-CoV-2 RNA and proteins in the brainstem. The brainstem is also highly prone to damage from pathological immune or vascular activation, which has also been observed in autopsy of COVID-19 cases. The second part concerns functions of the brainstem that overlap with symptoms of long-COVID. The brainstem contains numerous distinct nuclei and subparts that regulate the respiratory, cardiovascular, gastrointestinal, and neurological processes, which can be linked to long-COVID. As neurons do not readily regenerate, brainstem dysfunction may be long-lasting and, thus, is long-COVID. Indeed, brainstem dysfunction has been implicated in other similar disorders, such as chronic pain and migraine and myalgic encephalomyelitis or chronic fatigue syndrome.

Dual midbrain and forebrain origins of thalamic inhibitory interneurons.

The ubiquitous presence of inhibitory interneurons in the thalamus of primates contrasts with the sparsity of interneurons reported in mice. Here, we identify a larger than expected complexity and distribution of interneurons across the mouse thalamus, where all thalamic interneurons can be traced back to two developmental programmes: one specified in the midbrain and the other in the forebrain. Interneurons migrate to functionally distinct thalamocortical nuclei depending on their origin: the abundant, midbrain-derived class populates the first and higher order sensory thalamus while the rarer, forebrain-generated class is restricted to some higher order associative regions. We also observe that markers for the midbrain-born class are abundantly expressed throughout the thalamus of the New World monkey marmoset. These data therefore reveal that, despite the broad variability in interneuron density across mammalian species, the blueprint of the ontogenetic organisation of thalamic interneurons of larger-brained mammals exists and can be studied in mice.

Reduced thalamic resting-state functional connectivity and impaired cognition in acute abstinent heroin users.

As a critical component of cortico‐striato‐thalamo‐cortical loop in addiction, our understanding of the thalamus in impaired cognition of heroin users (HU) has been limited. Due to the complex thalamic connection with cortical and subcortical regions, thalamus was divided into prefrontal (PFC), occipital (OC), premotor, primary motor, sensory, temporal, and posterior parietal association subregions according to white matter tractography. We adopted seven subregions of bilateral thalamus as regions of interest to systematically study the implications of distinct thalamic nuclei in acute abstinent HU. The volume and resting‐state functional connectivity (RSFC) differences of the thalamus were investigated between age‐, gender‐, and alcohol‐matched 37 HU and 33 healthy controls (HCs). Trail making test‐A (TMT‐A) was adopted to assess cognitive function deficits, which were then correlated with neuroimaging findings. Although no significant different volumes were found, HU group showed decreased RSFC between left PFC_thalamus and middle temporal gyrus as well as between left OC_thalamus and inferior frontal gyrus and supplementary motor area relative to HCs. Meanwhile, the higher TMT‐A scores in HU were negatively correlated with PFC_thalamic RSFC with inferior temporal gyrus, fusiform, and precuneus. Craving scores were negatively correlated with OC_thalamic RSFC with accumbens, hippocampus, and insula. Opiate Withdrawal Scale scores were negatively correlated with left PFC/OC_thalamic RSFC with orbitofrontal cortex and medial PFC. We indicated two thalamus subregions separately involvement in cognitive control and craving to reveal the implications of thalamic subnucleus in pathology of acute abstinent HU.

Solid-state NMR studies of internuclear correlations for characterizing catalytic materials.

Understanding the nature of heterogeneous catalysts is critical for the rational design of highly active catalysts, which necessitates in-depth characterization of the structure and properties of catalysts as well as reaction mechanisms. Solid-state NMR correlation spectroscopy is becoming increasingly recognized as a powerful tool in the study of catalysts and catalytic reactions because of its capability to provide atomic-level insights into the structure, interaction and dynamics of molecules by establishing connectivity and proximity between the same or distinct nuclei. This tutorial review focuses on the fundamentals and state-of-the-art applications of solid-state NMR correlation techniques to structural characterization of catalytic materials including zeolites, metal oxides, organometallic complexes and MOFs as well as relevant studies regarding synthesis, synergistic catalysis, host-guest interactions and reaction mechanisms. Various correlation NMR methods that have been employed to address the challenging issues in heterogeneous catalysis are highlighted. This review concludes with outlooks on the promising applications and potential developments of solid-state NMR correlation spectroscopy in catalytic materials.

Efficient Generation of Functional Hepatocytes from Human Induced Pluripotent Stem Cells for Disease Modeling and Disease Gene Discovery.

In vitro hepatocyte cell models are being used to study the pathogenesis of liver disease and in the discovery and preclinical stages of drug development. The culture of hepatic cell lines and primary hepatocytes as in vitro cell models has been carried out for several decades. However, hepatic cell lines (hepatic carcinoma generated or immortalized) have limited accuracy when recapitulating complex physiological functions of the liver. Additionally, primary hepatocytes sourced from human cadavers or medical biopsies are difficult to obtain due to sourcing limitations, particularly for large-scale population studies or in applications requiring large number of cells. Hepatocyte cultures differentiated from human embryonic stem cells (ESCs) and induced pluripotent stem cell (iPSCs) overcome in large part the limitations of traditional hepatocyte in vitro models. In this chapter, we described an efficient protocol routinely used in our laboratory to differentiate human iPSCs into functional hepatocyte cultures for in vitro modeling of liver function and disease. The protocol uses a three-stage differentiation strategy to generate functional hepatocytes from human iPSCs. The differentiated cells show characteristic hepatocyte morphology including flat and polygonal shape, distinct round nuclei, and presence of biliary canaliculi and they express hepatic markers alpha-fetoprotein (AFP), albumin (ALB), E-cadherin (CHD1), hepatocyte nuclear factor 4 alpha (HNF4α), and actin.

Electronic Structure of the Primary Electron Donor P700+• in Photosystem I Studied by Multifrequency HYSCORE Spectroscopy at X- and Q-Band.

The primary electron donor P700 of the photosystem I (PSI) is a heterodimer consisting of two chlorophyll molecules. A series of electron-transfer events immediately following the initial light excitation leads to a stabilization of the positive charge by its cation radical form, P700+•. The electronic structure of P700+• and, in particular, its asymmetry with respect to the two chlorophyll monomers is of fundamental interest and is not fully understood up to this date. Here, we apply multifrequency X- (9 GHz) and Q-band (35 GHz) hyperfine sublevel correlation (HYSCORE) spectroscopy to investigate the electron spin density distribution in the cation radical P700+• of PSI from a thermophilic cyanobacterium Thermosynechococcus elongatus. Six 14N and two 1H distinct nuclei have been resolved in the HYSCORE spectra and parameters of the corresponding nuclear hyperfine and quadrupolar hyperfine interactions were obtained by combining the analysis of HYSCORE spectral features with direct numerical simulations. Based on a close similarity of the nuclear quadrupole tensor parameters, all of the resolved 14N nuclei were assigned to six out of total eight available pyrrole ring nitrogen atoms (i.e., four in each of the chlorophylls), providing direct evidence of spin density delocalization over the both monomers in the heterodimer. Using the obtained experimental values of the 14N electron-nuclear hyperfine interaction parameters, the upper limit of the electron spin density asymmetry parameter is estimated as RA/Bupper = 7.7 ± 0.5, while a tentative assignment of 14N observed in the HYSCORE spectra yields RB/A = 3.1 ± 0.5.

Molecular Dynamics Study of Bubble Nucleation on an Ideally Smooth Substrate.

Questions regarding bubble nucleation on an ideally smooth surface are seemingly endless, but it can not be adequately verified yet because of the scale limitation (microscopic scale). Hence, in this study, bubble nucleation on an ideally smooth substrate is explored using the molecular dynamics simulation method. An ideally smooth hydrophilic platinum substrate at 145 K is conducted to heat the simple L-J liquid argon. Results show that a visible bubble nucleus successfully forms on the ideally smooth substrate without any additional disturbance, which is common in boiling studies using the traditional numerical simulation methods. However, the nucleation position is unpredictable. At the atomic level, the thermal energy transfer from an ideally smooth substrate to liquid atoms is inhomogeneous due to atomic inhomogeneous distribution and irregular movement, which are the key influencing factors for achieving bubble nucleation. The inhomogeneity will be highlighted with the heating process. As a result, some local liquid atoms near the ideally smooth surface absorb more thermal energy to overcome their potential barrier at a specific moment, causing the emergence of a distinct nucleus there. Furthermore, nanostructure substrates are introduced to make a comparison with the smooth substrate in bubble nucleation. There is no significant difference in the inception temperature of nucleation between the ideally smooth and nanostructure substrates, but the latter has better performance in improving the bubble nucleation rate.

Naegleria Fowleri Diagnosed with Hospital Autopsy in a Toddler: A Case Study

Abstract Casestudy Naegleria fowleri, an amoeba, is typically found in warm freshwater lakes, ponds, rivers and hot springs. It is responsible for causing the incredibly rare and lethal central nervous system infection called Primary Amoebic Meningoencephalitis (PAM). In the United States, 145 confirmed cases have been documented since 1962. Most cases are associated with freshwater lakes, ponds and reservoirs, while only a handful have been linked to artificial recreational venues such as pools, interactive water play-grounds, and spas. In addition to highlighting a rare amoebic disease, this case illustrates the continued importance of hospital autopsies especially given recent ruling to eliminate the autopsy requirement by the Centers for Medicare and Medicaid Services. Results An otherwise healthy toddler had upper respiratory symptoms and otitis media days after returning from an artificial recreational water venue, becoming increasingly lethargic and febrile over the next few days. At the hospital, cerebrospinal fluid (CSF) abnormalities were suggestive but not consistent with bacterial meningitis. A meningoencephalitis panel, a Computed Tomograph (CT) scan of the head, and chest-x-ray were negative for abnormalities. Appropriate antimicrobial therapy was initiated. Three days after hospital admission, his symptoms worsened including development of dysconjugate gaze and signs of cerebellitis. He became increasingly hemodynamically unstable, suffered an arrest, and passed away days later. Conclusion Since this death did not fall under the state’s statutes mandating medicolegal autopsy, a hospital- requested autopsy was performed. Cerebral edema and a light gray to light green exudate was along the inferior and lateral left temporal lobe, brain stem, and cerebellum. An exuberant lymphoplasmacytic infiltrate with scattered polymorphonuclear leukocytes expanded the meninges. Small histiocyte-like cells with distinct eccentric nuclei and granular, vacuolated cytoplasm, confirmed by Centers for Disease Control and Prevention (CDC) to be Naegleria fowleri, were best visualized in the Virchow-Robin spaces and deeper parenchyma.

PRIMARY MEDIASTINAL SEMINOMA FOUND ON EVALUATION FOR WEIGHT LOSS

SESSION TITLE: Medical Student/Resident Disorders of the Mediastinum Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Extragonadal germ cell tumors (GCTs) typically arise in midline locations such as mediastinum and retroperitoneum. They are formed either due to failure of primordial germ cells to migrate to the gonadal ridges [1] or reverse migration of the transformed germ cells in the testes [2]. Mediastinal seminomas are rare tumors constituting about 1/3rd of malignant mediastinal GCTs and 2-4 percent of mediastinal masses [3]. CASE PRESENTATION: A 55-year-old man with a history of active smoking (½ pack cigarettes per day), hepatitis C, bipolar disorder, prior alcohol/intravenous drug use (heroin and cocaine) presented with shortness of breath and 50-pound weight loss. Chest computed tomography (CT) revealed a 3.0 x 1.1 cm para-aortic lymph node. Positron emission tomography (PET/CT) scan showed hypermetabolic activity (maximum standardized uptake value of 10). Bronchoscopy with EBUS (endoscopic ultrasound) and mediastinoscopy were considered as methods to obtain tissue but discarded due to the location of the mass. He underwent a left Video-assisted thoracoscopic surgery (VATS) which showed seminoma. H&E (hematoxylin and eosin) slides revealed pale tumor cells with distinct nuclei and prominent central nucleoli in a background of lymphocytic infiltrate. The tumor cells stained positive for germ cell markers CD117, Oct 3/4 and Sall 4; but were negative for melanoma markers (Mart1a, S100), as well as CK20, CK7, Pancytokeratin, CD30, CD15, TTF1 and CDX2. DISCUSSION: Mediastinal seminomas occur mainly in men aged 20 to 40 years. They are typically slow growing and can be very bulky by the time they cause symptoms. Serum beta subunit of human chorionic gonadotropin (beta-hCG) is elevated in approximately one-third of patients. They do not produce alpha-fetoprotein (AFP). Ultrasound is advised in all cases to evaluate for any testicular primary. Seminomas are exquisitely sensitive to both cisplatin-based chemotherapy and radiotherapy (RT) but local control with surgery and RT only have modest success due to their typically later presentation. The commonly used chemotherapy regimens are 3 cycles of bleomycin/etoposide/cisplatin (BEP) or 4 cycles of etoposide/cisplatin (EP) (in patients who have previously received RT, who have underlying lung disease or age more than 50 years to avoid bleomycin lung toxicity). Long-term disease-free survival is achieved in roughly 90 percent of patients treated with chemotherapy. CONCLUSIONS: Primary mediastinal seminoma is a malignant extragonadal GCT most commonly found in the anterior mediastinum. Usually, young men in their 20-40s present with large 4-11cm anterior mediastinal masses which cause symptoms by compressing local structures. Or, as in our case, they are found incidentally. Surgery/RT can be considered but many patients present late so local control is not possible. However, these tumors respond well to chemotherapy with complete response rates of 90% Reference #1: Intracranial germ cell tumors: a comprehensive review of proposed embryologic derivation; Glenn OA, Barkovich AJ; Pediatr Neurosurg. 1996;24(5):242; PMID 8933567 Reference #2: Genetics and biology of adult human male germ cell tumors; Chaganti RS, Houldsworth J; Cancer Res. 2000;60(6):1475; PMID 10749107 Reference #3: Primary germ cell tumors of the mediastinum: II. Mediastinal seminomas--a clinicopathologic and immunohistochemical study of 120 cases; Moran CA, Suster S, Przygodzki RM, Koss MN; Cancer. 1997;80(4):691; PMID 9264352 DISCLOSURES: No relevant relationships by William Han, source=Web Response No relevant relationships by Sahib Singh, source=Web Response

Molecular Fingerprint and Developmental Regulation of the Tegmental GABAergic and Glutamatergic Neurons Derived from the Anterior Hindbrain

Tegmental nuclei in the ventral midbrain and anterior hindbrain control motivated behavior, mood, memory, and movement. These nuclei contain inhibitory GABAergic and excitatory glutamatergic neurons, whose molecular diversity and development remain largely unraveled. Many tegmental neurons originate in the embryonic ventral rhombomere 1 (r1), where GABAergic fate is regulated by the transcription factor (TF) Tal1. We used single-cell mRNA sequencing of the mouse ventral r1 to characterize the Tal1-dependent and independent neuronal precursors. We describe gene expression dynamics during bifurcation of the GABAergic and glutamatergic lineages and show how active Notch signaling promotes GABAergic fate selection in post-mitotic precursors. We identify GABAergic precursor subtypes that give rise to distinct tegmental nuclei and demonstrate that Sox14 and Zfpm2, two TFs downstream of Tal1, are necessary for the differentiation of specific tegmental GABAergic neurons. Our results provide a framework for understanding the development of cellular diversity in the tegmental nuclei.

Abstract 6019: Identification of the neo-genesis of glioblastoma stem cells using label-free quantitative phase imaging

Abstract Introduction: Glioblastoma (GBM) is the most aggressive neurological cancer with a very poor prognosis due to its propensity to regenerate after medical interventions. Our experimental model is U87-MG cells, which contain subsets of cancer stem cells (CSC) and have the unusual property of spontaneously forming neurospheres in culture. We are investigating the origins of these stem cells. Materials and Methods: We employ recently developed time label-free, time-lapse quantitative phase imaging (QPI) technology that allows precise quantification of the refractive index (RI) distributions on a sub-cellular level. These measurements are stored in 2D or 3D arrays which can be presented as images or videos at various resolutions. Cells were seeded into sealable culture Petrie dishes and imaged while maintaining appropriate environmental controls. Results: We first noted CSCs in late stage cultures in exploratory experiments, where they presented as small cells (10-15 um) compared to the 50-100 um range of mature U8-MR cells. Their refractive index (RI) is 1.42, compared to about 1.40 for the cytoplasm of mature cells. QPI technology sensitivity enables almost complete separation between the two cell types in RI histograms. We exemplify a grouping of cells in an 80 um2 field of view, tracked in multiple time segments ranging from 20 minutes to 12 hours over a period of about 18 hours, containing a mature U87 which serves as a reference marker. Around this cell, there are 3 distinct pro-stem (PS) cells 12 to 16 um in size: PS-1 with numerous 0.5 um particles in the size range of mitochondria, PS-2 with a nucleus with nucleoli but no nuclear membrane, and PS-3 with a distinct nucleus, nucleoli, and cytosol. The cells are all connected in a network of nanotubes and tunnels. PS-1 and PS-2 are not very active in the early analysis, but they eventually move together and appear to fuse while still maintaining their individual shapes. PS-3 is very actively interacting with another cell on the border of the analysis window. It is extending and retracting a tube and is apparently moving materials both to and away from the other cell in a very regular and linear fashion, suggesting a primitive form of transcription. Discussion: The processes we observed are consistent with tumor stem cell generation by autophagy, mitophagy, and catabolization followed by reprograming of the remnants and formation of neoplastic stem cells. The novelty of our approach is determined by technical capabilities of our QPI platforms, which is non-invasive label-free approach coupled with ultra-high-resolution analysis, previously unobtainable in traditional time-lapse imaging systems. Citation Format: Ed Luther, Livia P. Mendes, Vladimir P. Torchilin. Identification of the neo-genesis of glioblastoma stem cells using label-free quantitative phase imaging [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6019.

Endogenous Opsin 3 (OPN3) Protein Expression in the Adult Brain Using a Novel OPN3-mCherry Knock-In Mouse Model.

The opsins have been studied extensively for their functions in visual phototransduction; however, the mechanisms underlying extraocular opsin signaling remain poorly understood. The first mammalian extraocular opsin to be discovered, opsin 3 (OPN3), was found in the brain more than two decades ago, yet its function remains unknown. A significant hindrance to studying OPN3 has been a lack of specific antibodies against mammalian OPN3, resulting in an incomplete understanding of its expression in the brain. Although Opn3 promoter-driven reporter mice have been generated to examine general OPN3 localization, they lack the regulated expression of the endogenous protein and the ability to study its subcellular localization. To circumvent these issues, we have created a knock-in OPN3-mCherry mouse model in which the fusion protein OPN3-mCherry is expressed under the endogenous Opn3 promoter. Viable and fertile homozygotes for the OPN3-mCherry allele were used to create an extensive map of OPN3-mCherry expression across the adult mouse brain. OPN3-mCherry was readily visualized in distinct layers of the cerebral cortex (CTX), the hippocampal formation (HCF), distinct nuclei of the thalamus, as well as many other regions in both neuronal and non-neuronal cells. Our mouse model offers a new platform to investigate the function of OPN3 in the brain.

Nuclear organization and morphology of catecholaminergic neurons and certain pallial terminal networks in the brain of the Nile crocodile, Crocodylus niloticus

In the current study, we use tyrosine hydroxylase (TH) immunohistochemistry to detail the nuclear parcellation and cellular morphology of neurons belonging to the catecholaminergic system in the brain of the Nile crocodile. In general, our results are similar to that found in another crocodilian (the spectacled caiman) and indeed other vertebrates, but certain differences of both evolutionary and functional significance were noted. TH immunopositive (TH+) neurons forming distinct nuclei were observed in the olfactory bulb (A16), hypothalamus (A11, A13-15), midbrain (A8-A10), pons (A5-A7) and medulla oblongata (area postrema, C1, C2, A1, A2), encompassing the more commonly observed nuclear complexes of this system across vertebrates. In addition, TH + neurons forming distinct nuclei not commonly identified in vertebrates were observed in the anterior olfactory nucleus, the pretectal nuclear complex, adjacent to the posterior commissure, and within nucleus laminaris, nucleus magnocellularis lateralis and the lateral vestibular nucleus. Palely stained TH + neurons were observed in some of the serotonergic nuclei, including the medial and lateral divisions of the superior raphe nucleus and the inferior raphe and inferior reticular nucleus, but not in other serotonergic nuclei. In birds, a high density of TH + fibres and pericellular baskets in the dorsal ventricular ridge marks the location of the nidopallium caudolaterale (NCL), a putative avian analogue of mammalian prefrontal cortex. In the dorsal ventricular ridge (DVR) of the crocodile a small region in the caudolateral anterior DVR (ADVRcl) revealed a slightly higher density of TH + fibres and some pericellular baskets (formed by only few TH + fibres). These results are discussed in an evolutionary and functional framework.

Amygdala pathology in amyotrophic lateral sclerosis and primary lateral sclerosis

Temporal lobe studies in motor neuron disease overwhelmingly focus on white matter alterations and cortical grey matter atrophy. Reports on amygdala involvement are conflicting and the amygdala is typically evaluated as single structure despite consisting of several functionally and cytologically distinct nuclei. A prospective, single-centre, neuroimaging study was undertaken to comprehensively characterise amygdala pathology in 100 genetically-stratified ALS patients, 33 patients with PLS and 117 healthy controls. The amygdala was segmented into groups of nuclei using a Bayesian parcellation algorithm based on a probabilistic atlas and shape deformations were additionally assessed by vertex analyses. The accessory basal nucleus (p = .021) and the cortical nucleus (p = .022) showed significant volume reductions in C9orf72 negative ALS patients compared to controls. The lateral nucleus (p = .043) and the cortico-amygdaloid transition (p = .024) were preferentially affected in C9orf72 hexanucleotide carriers. A trend of total volume reduction was identified in C9orf72 positive ALS patients (p = .055) which was also captured in inferior-medial shape deformations on vertex analyses. Our findings highlight that the amygdala is affected in ALS and our study demonstrates the selective involvement of specific nuclei as opposed to global atrophy. The genotype-specific patterns of amygdala involvement identified by this study are consistent with the growing literature of extra-motor clinical features. Mesial temporal lobe pathology in ALS is not limited to hippocampal pathology but, as a key hub of the limbic system, the amygdala is also affected in ALS.

MR Susceptibility Imaging with a Short TE (MR-SISET): A Clinically Feasible Technique to Resolve Thalamic Nuclei.

The thalamus consists of several functionally distinct nuclei, some of which serve as targets for functional neurosurgery. Visualization of such nuclei is a major challenge due to their low signal contrast on conventional imaging. We introduce MR susceptibility imaging with a short TE, leveraging susceptibility differences among thalamic nuclei, to automatically delineate 15 thalamic subregions. The technique has the potential to enable direct targeting of thalamic nuclei for functional neurosurgical guidance.

Brain functional abnormalities in the amygdala subregions is associated with anxious depression

BackgroundFunctional neuroimaging studies have provided strong support for the critical role the amygdala plays in emotional processing. The amygdala is composed of three primary distinct nuclei that have different functions in emotional regulation. Anxious depression (AD) was considered as a common dimensional symptom of Major Depressive Disorder (MDD). However, the neuroimaging basis of this special MDD subtype remains largely unknown. Therefore, it is necessary to study the functional connectivity of the amygdala's subregions in AD patients. MethodsEighty-three patients with AD, 70 non-anxious depression (NAD) patients, and 62 healthy controls were collected. Age and gender were well-matched. The functional connectivity of three amygdala subregions, including centromedial (CM), laterobasal (LB), and superficial (SF), were compared among the AD, NAD, and HC groups. The correlation between functional connectivity in the amygdala subregions and the HAMD factor scores were further analyzed. ResultsPatients with AD showed decreased functional connectivity between the right CM/LB and the right middle frontal gyrus relative to the NAD group. The NAD patients showed decreased functional connectivity between the right precentral gyrus and the right CM/SF compared to the HC group. The functional connectivity between the right CM and the right middle frontal gyrus was negatively correlated with the anxiety/somatization factor. ConclusionThe functional connectivity between the right CM/LB and the right middle frontal gyrus might be the neurobiological mechanism of anxious depression. The FC between the right CM and the right middle frontal gyrus may help to explain the special clinical feature of the AD patients.

Topological atlas of the hypothalamus in adult rhesus monkey

The prosomeric model explains the embryological development of the central nervous system (CNS) shared by all vertebrates as a Bauplan. As a primary event, the early neural plate is patterned by intersecting longitudinal plates and transverse segments, forming a mosaic of progenitor units. The hypothalamus is specified by three prosomeres (hp1, hp2, and the acroterminal domain) of the secondary prosencephalon with corresponding alar and basal plate parts, which develop apart from the diencephalon. Mounting evidence suggests that progenitor units within alar and basal plate parts of hp1 and hp2 give rise to distinct hypothalamic nuclei, which preserve their relative invariant positioning (topology) in the adult brain. Nonetheless, the principles of the prosomeric model have not been applied so far to the hypothalamus of adult primates. We parcellated hypothalamic nuclei in adult rhesus monkeys (Macaca mulatta) using various stains to view architectonic boundaries. We then analyzed the topological relations of hypothalamic nuclei and adjacent hypothalamic landmarks with homology across rodent and primate species to trace the origin of adult hypothalamic nuclei to the alar or basal plate components of hp1 and hp2. We generated a novel atlas of the hypothalamus of the adult rhesus monkey with developmental ontologies for each hypothalamic nucleus. The result is a systematic reinterpretation of the adult hypothalamus whose prosomeric ontology can be used to study relationships between the hypothalamus and other regions of the CNS. Further, our atlas may serve as a tool to predict causal patterns in physiological and pathological pathways involving the hypothalamus.