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Microscopic neuroanatomy of limbic system and basal forebrain on MRI is complex and is a terra incognita for many radiologists, clinicians, and neuroscientists. Interestingly, most of the important structures/at least anatomical regions containing these structures demonstrable on cadaveric and surgical dissections can be identified on clinical MRI, with 3T being much better than 1.5T. This article teaches the practical MRI identification of these structures which will greatly help in evaluating complex ailments like temporal lobe epilepsy, Alzheimer dementia, and other neuropsychiatric disorders. This knowledge will also aid in accurate reporting of tumor spread along the white matter fasciculi in the temporal stem/basal forebrain region. Limbic system includes the mesial temporal structures and their connections, piriform cortex including "area tempestas," and the septal area comprising of subcallosal area and paraterminal gyrus. Basal forebrain includes structures like substantia innominata with basal nucleus of Meynert, diagonal gyrus/diagonal band of Broca, and nucleus accumbens lying in between the anterior perforated substance inferiorly and the anterior commissure superiorly., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The Papez circuit was first described as the anatomic basis of emotion. Subsequent studies consolidated recognition of its limbic activities but showed a more important role in memory. Anatomic dissections and advanced neuroimaging have deepened our understanding of the various interconnections and white matter tracts present in this circuit. The aim of our study is to describe the anatomy of the Papez circuit through cadaveric dissection with correlation to ultrahigh-field magnetic resonance imaging (MRI) and MRI tractography., Methods: White fiber dissection was performed on 5 cadaveric human brain hemispheres. The Papez circuit was dissected mediolaterally to show its anatomy and relation to other nuclei and tracts. Open-source MRI tractography data from the Human Connectome Project is combined with ultrahigh resolution, 7T structural MRI, and 17.6T diffusion tractography to further show the anatomy., Results: The network connecting the anterior and posterior cingulate, entorhinal cortex, hippocampus, fimbria, dentate gyrus, fornix, mammillary bodies, and anterior thalamus was described using white matter fiber dissection and compared with MRI tractography and ultrahigh-field structural and diffusion MRI. We showed for the first time (through portmortem dissection) fibers directly connecting the anterior thalamic nucleus and the subgenual cingulate via the septal area., Conclusions: The description of the anatomy of the Papez circuit through cadaveric dissection and comparisons with advanced neuroimaging studies allow a better understanding of its three-dimensional spatial layout, in addition to showing new areas of connectivity with adjacent structures and possibilities for surgical approaches or stimulation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Insular cortex is a core hub involved in multiple cognitive and socio-affective processes. Yet, the anatomical mechanisms that explain how it is involved in such a diverse array of functions remain incompletely understood. Here, we tested the hypothesis that changes in myeloarchitecture across the insular cortex explain how it can be involved in many different facets of cognitive function. Detailed intracortical profiling, performed across hundreds of insular locations on the basis of myelin-sensitive magnetic resonance imaging (MRI), was compressed into a lower-dimensional space uncovering principal axes of myeloarchitectonic variation. Leveraging two datasets with different high-resolution MRI contrasts, we obtained robust support for two principal dimensions of insular myeloarchitectonic differentiation in vivo, one running from ventral anterior to posterior banks and one radiating from dorsal anterior towards both ventral anterior and posterior subregions. Analyses of post mortem 3D histological data showed that the antero-posterior axis was mirrored in cytoarchitectural markers, even when controlling for sulco-gyral folding. Resting-state functional connectomics in the same individuals and ad hoc meta-analyses showed that myelin gradients in the insula relate to diverse affiliation to macroscale intrinsic functional systems, showing differential shifts in functional network embedding across each myelin-derived gradient. Collectively, our findings offer a novel approach to capture structure-function interactions of a key node of the limbic system, and suggest a multidimensional structural basis underlying the diverse functional roles of the insula., (Copyright © 2020. Published by Elsevier Inc.)

The limbic system is a phylogenetically old, behaviorally defined system that serves as a center for emotions. It controls the expression of anger, fear, and joy and also influences sexual behavior, vegetative functions, and memory. The system comprises a collection of tel-, di-, and mesencephalic structures whose components have evolved and increased over time. Previous animal research indicates that the anterior nuclear group of the thalamus (ANT), as well as the habenula (Hb) and the adjacent mediodorsal nucleus (MD) each play a vital role in the limbic circuitry. Accordingly, diffusion imaging data of 730 subjects obtained from the Human Connectome Project and the masks of six nuclei (anterodorsal, anteromedial, anteroventral, lateral dorsal, Hb, and MD) served as seed regions for a direct probabilistic tracking to the rest of the brain using diffusion-weighted imaging. The results revealed that the ANT nuclei are part of the limbic and the memory system as they mainly connect via the mammillary tract, mammillary body, anterior commissure, fornix, and retrosplenial cortices to the hippocampus, amygdala, medio-temporal, orbito-frontal and occipital cortices. Furthermore, the ANT nuclei showed connections to the mesencephalon and brainstem to varying extents, a pattern rarely described in experimental findings. The habenula-usually defined as part of the epithalamus-was closely connected to the tectum opticum and seems to serve as a neuroanatomical hub between the visual and the limbic system, brainstem, and cerebellum. Finally, in contrast to experimental findings with tracer studies, directly determined connections of MD were mainly confined to the brainstem, while indirect MD fibers form a broad pathway connecting the hippocampus and medio-temporal areas with the mediofrontal cortex.

The human hypothalamus is at the center of the human limbic system anatomically and physiologically. The hypothalamus plays pivotal roles in controlling autonomic responses and instinctive behaviors such as regulating fear, aggression, learning, feeding behavior, circadian rhythm, and reproductive activities. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. The inhibitory effect of the cerebral cortex on the hypothalamus in many autonomic responses, suggests the presence of direct connection between the cortex and hypothalamic nuclei. While, there is ample information to support the cortico-hypothalamic association between the prefrontal cortex and hypothalamic nuclei, the information regarding a direct posterior cortico-hypothalamic alliance is scant. The visuosensory information may be crucial for the limbic system to regulate some of the important limbic functions. Multiple dissection animal studies revealed direct posterior cortical connectivity with the hypothalamic nuclei. However, a direct cortico-hypothalamic connectivity from the parieto-occipital cortices has not been revealed in the human brain yet. Diffusion weighted imaging (DWI) may be helpful in better visualizing the anatomy of this direct posterior cortico-limbic connectivity noninvasively in the human brain. We studied 30 healthy human subjects. Using a high-spatial and high angular resolution diffusion weighted tractography technique, for the first time, we were able to delineate and reconstruct the trajectory of the parieto-occipito-hypothalamic tract., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Mental health problems often emerge in adolescence and are associated with reduced gray matter thickness or volume in the prefrontal cortex (PFC) and limbic system and reduced fractional anisotropy (FA) and increased mean diffusivity (MD) of white matter linking these regions. However, few studies have investigated whether internalizing and externalizing behavior are associated with brain structure in children and adolescents without mental health disorders, which is important for understanding the progression of symptoms. 67 T1-weighted and diffusion tensor imaging datasets were obtained from 48 typically developing participants aged 6-16 years (37M/30F; 19 participants had two visits). Volume was calculated in the prefrontal and limbic structures, and diffusion parameters were assessed in limbic white matter. Linear mixed effects models were used to compute associations between brain structure and internalizing and externalizing behavior, assessed using the Behavioral Assessment System for Children (BASC-2) Parent Rating Scale. Internalizing behavior was positively associated with MD of the bilateral cingulum. Gender interactions were found in the cingulum, with stronger positive relationships between MD and internalizing behavior in females. Externalizing behavior was negatively associated with FA of the left cingulum, and the left uncinate fasciculus showed an age-behavior interaction. No relationships between behavior and brain volumes survived multiple comparison correction. These results show altered limbic white matter FA and MD related to sub-clinical internalizing and externalizing behavior and further our understanding of neurological markers that may underlie risk for future mental health disorders.

Though adolescence is a time of emerging sex differences in emotions, sex-related differences in the anatomy of the maturing brain has been under-explored over this period. The aim of this study was to investigate whether puberty and sexual differentiation in brain maturation could explain emotional differences between girls and boys during adolescence. We adapted a dedicated longitudinal pipeline to process structural and diffusion images from 335 typically developing adolescents between 14 and 16 years. We used voxel-based and Regions of Interest approaches to explore sex and puberty effects on brain and behavioral changes during adolescence. Sexual differences in brain maturation were characterized by amygdala and hippocampal volume increase in boys and decrease in girls. These changes were mediating the sexual differences in positive emotional regulation as illustrated by positive attributes increase in boys and decrease in girls. Moreover, the differential maturation rates between the limbic system and the prefrontal cortex highlighted the delayed maturation in boys compared to girls. This is the first study to show the sex effects on the differential cortico/subcortical maturation rates and the interaction between sex and puberty in the limbic system maturation related to positive attributes, reported as being protective from emotional disorders., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The limbic system encompasses a collection of brain areas primarily involved in higher cognitive and emotional processing. Altered function in the limbic circuitry may play a major role in various psychiatric disorders. This study aims to provide a high-quality ex vivo diffusion-weighted MRI (DWI) tractographic overview of the Göttingen minipig limbic system pathways, which are currently not well described. This may facilitate future translational large animal studies. The study used previously obtained post-mortem DWI scans in 3 female Göttingen minipigs aging 11-15 months. The tractography performed on the DWI data set was made using a probabilistic algorithm, and regions of interest (ROIs) were defined in accordance with a histological atlas. The investigated pathways included the fornix, mammillothalamic tract, stria terminalis, stria medullaris, habenulo-interpeduncular tract, and cingulum. All the investigated limbic connections could be visualized with a high detail yielding a comprehensive three-dimensional overview, which was emphasized by the inclusion of video material. The minipig limbic system pathways displayed using tractography closely resembled what was previously described in both human studies and neuronal tracing studies from other mammalian species. We encountered well-known inherent methodological challenges of tractography, e.g., partial volume effects and complex white matter regions, which may have contributed to derouted false-positive streamlines and the failure to visualize some of the minor limbic pathway ramifications. This underlines the importance of preexisting anatomical knowledge. Conclusively, we have, for the first time, provided an overview and substantial insight of the Göttingen minipig limbic system.

Degree centrality is a widely used measure in complex networks. Within the brain, degree relates to other topological features, with high-degree nodes (i.e., hubs) exhibiting high betweenness centrality, participation coefficient, and within-module z-score. However, increasing evidence from neuroanatomical and predictive processing literature suggests that topological properties of a brain network may also be impacted by topography, that is, anatomical (spatial) distribution. More specifically, cortical limbic areas (agranular and dysgranular cortices), which occupy an anatomically central position, have been proposed to be topologically central and well suited to initiate predictions in the cerebral cortex. We estimated anatomical centrality and showed that it positively correlated with betweenness centrality, participation coefficient, and communicability, analogously to degree. In contrast to degree, however, anatomical centrality negatively correlated with within-module z-score. Our data suggest that degree centrality and anatomical centrality reflect distinct contributions to cortical organization. Whereas degree would be more related to the amount of information integration performed by an area, anatomical centrality would be more related to an area's position in the predictive hierarchy. Highly anatomically central areas may function as "high-level connectors," integrating already highly integrated information across modules. These results are consistent with a high-level, domain-general limbic workspace, integrated by highly anatomically central cortical areas., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The subthalamic nucleus (STN) receives direct cortical inputs which constitute the so-called hyperdirect pathway. In monkeys, motor cortices innervate the whole extent of the STN whereas limbic cortices innervate only its anteromedial part extending more medially outside the nucleus. Tractography studies in humans have also identified motor cortical inputs to the STN, but little is known about the associative and limbic cortical projections. Therefore, the aim of this study was to investigate the anatomo-functional organization of the cortical projections to the STN and to the adjacent medial subthamic region (MSR). We used diffusion-weighted imaging-based tractography acquired from 30 subjects from the Human Connectome Project. We performed a whole-brain probabilistic tractography using MRTrix and extracted streamlines of interest between 39 cortical masks and both the STN and the MSR to provide track-density maps. Agglomerative clustering method was used to classify the voxels of the regions of interest. We found that the STN receives major inputs from the sensorimotor cortices and few inputs from the limbic cortices. On the other hand, the MSR receives mainly cortical limbic projections and few from the sensorimotor cortices. Weak connections were found between the associative cortices and both the STN and the MSR. We found a dominant motor cluster located in the posterolateral STN, a limbic cluster located medially in the MSR, and an intermediate motor-limbic cluster in between. Our findings show that the hyperdirect pathway is anatomo-functionally organized with a poor participation of associative cortices.

Introduction: In-class courses are deserted by medical students who tend to find it more beneficial to study in books and through online material. New interactive teaching methods, such as serious games increase both performance and motivation. We developed and assessed a new teaching method for neurological semiology using the "Hat Game" as a basis., Methods: In this game, two teams of second-year medical students are playing against one another. The game is played with a deck of cards. A neurological symptom or sign is written on each card. Each team gets a predefined period of time to guess as many words as possible. One member is the clue-giver and the others are the guessers. There are three rounds: during the first round, the clue-giver uses any descriptive term he wants and as many as he wants to make his team guess the maximum number of words within the allocated time. During the second round, the clue-giver can only choose one clue-word and, during the third round, he mimes the symptom or sign. The team that has guessed the most cards wins the game. To assess the efficacy of this learning procedure, multiple choices questions (MCQs) were asked before and after the game. Exam results of second-year students on their final university Neurology exam were analyzed. A satisfaction survey was proposed to all participating students., Results: Among 373 students, 121 volunteers (32.4%) were enrolled in the "Neurology Hat Game" and 112 attended the game. One hundred and seven of the 112 students completed the MCQs with a significant improvement in their responses after the game (P<0.001). The 112 students who completed the satisfaction self-administered questionnaire were very satisfied with this funny new teaching method., Conclusions: Teaching neurological semiology via the "Hat Game" is an interesting method because it is student-centered, playful and complementary to the lecturer-centered courses. A randomized controlled study would be necessary to confirm these preliminary results., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Previous research has demonstrated significant relationships between obesity and brain structure. Both phenotypes are heritable, but it is not known whether they are influenced by common genetic factors. We investigated the genetic etiology of the relationship between individual variability in brain morphology and BMIz using structural MRI in adolescent twins., Method: The sample (n = 258) consisted of 54 monozygotic and 75 dizygotic twin pairs (mean(SD) age = 13.61(0.505), BMIz = 0.608(1.013). Brain structure (volume and density of gray and white matter) was assessed using VBM. Significant voxelwise heritability of brain structure was established using the Accelerated Permutation inference for ACE models (APACE) program, with structural heritability varying from 15 to 97%, depending on region. Bivariate heritability analyses were carried out comparing additive genetic and unique environment models with and without shared genetics on BMIz and the voxels showing significant heritability in the APACE analyses., Results: BMIz was positively related to gray matter volume in the brainstem and thalamus and negatively related to gray matter volume in the bilateral uncus and medial orbitofrontal cortex, gray matter density in the cerebellum, prefrontal lobe, temporal lobe, and limbic system, and white matter density in the brainstem. Bivariate heritability analyses showed that BMIz and brain structure share ∼1/3 of their genes and that ∼95% of the phenotypic correlation between BMIz and brain structure is due to shared additive genetic influences. These regions included areas related to decision-making, motivation, liking vs. wanting, taste, interoception, reward processing/learning, caloric evaluation, and inhibition., Conclusion: These results suggested genetic factors are responsible for the relationship between BMIz and heritable BMIz related brain structure in areas related to eating behavior., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cortico-basal ganglia-thalamocortical loops are largely conceived as parallel circuits that process limbic, associative, and sensorimotor information separately. Whether and how these functionally distinct loops interact remains unclear. Combining genetic and viral approaches, we systemically mapped the limbic and motor cortico-basal ganglia-thalamocortical loops in rodents. Despite largely closed loops within each functional domain, we discovered a unidirectional influence of the limbic over the motor loop via ventral striatum-substantia nigra (SNr)-motor thalamus circuitry. Slice electrophysiology verifies that the projection from ventral striatum functionally inhibits nigro-thalamic SNr neurons. In vivo optogenetic stimulation of ventral or dorsolateral striatum to SNr pathway modulates activity in medial prefrontal cortex (mPFC) and motor cortex (M1), respectively. However, whereas the dorsolateral striatum-SNr pathway exerts little impact on mPFC, activation of the ventral striatum-SNr pathway effectively alters M1 activity. These results demonstrate an open cortico-basal ganglia loop whereby limbic information could modulate motor output through ventral striatum control of M1., Competing Interests: SA, JS, HL, XY, MI, PC, JW, TR, XJ No competing interests declared, (© 2019, Aoki et al.)

Broca's (1878) definition of the limbic lobe referred to its being located at the edge of the cerebral cortex, and Papez (1937) and MacLean (1990) welded a series of medial surface structures into what we now know as the limbic system. The last four decades of research have provided a wealth of detailed information on the connectivity and functions of the limbic system and one can only conclude that it is not a uniform and single system. The cingulate cortex itself has three major divisions: anterior primarily for emotion, middle mainly for response selection and feedback-guided decision making, and posterior/retrosplenial cortices for visuospatial orientation and assessing the self-relevance of objects and events. Each of these divisions has a different cytoarchitecture and set of connections. The cingulate observations lead to a new framework of limbic organization: three limbic subsystems that include the amygdala, orbitofrontal cortex, the insula, the hippocampus, and, of course, the cingulate cortex. This concept is expanded in terms of connectivity among them and the underlying functions of each subsystem. The three limbic subsystems considered here are the "anterior emotional subsystem," the "middle sensorimotor subsystem," and the "posterior cognitive spatial map subsystem" for localizing personally relevant objects and episodes. A defining characteristic of the anterior emotional subsystem is its input from the amygdala. Another interesting outcome of this analysis is that the middle hippocampus and anterior midcingulate cortex share a role in approach-avoidance decision making suggesting a potential for connectional synergy. Thus, the concept of "a" limbic system needs radical revision to accommodate a minimum of three limbic subsystems. As this approach was initiated by the three-part composition of the cingulate cortex, a finer-grain analysis of the cingulate region shows that six limbic subsystems may be a more accurate reflection of limbic organization., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this study, MRI and DTI were employed to examine subcortical volume and microstructural properties (FA, MD) of the limbic network, and their relationships with affect discrimination in 13 FL (6 right FL, M = 10.17 years; 7 left FL; M = 10.09) and 13 typically-developing children (TD; M = 10.16). Subcortical volume of the amygdala, hippocampus and thalamus and FA and MD of the fornix and anterior thalamic radiation (ATR) were examined. Results revealed no group differences across emotion-perception tasks or amygdalar volume. However, contrasting neuroanatomical patterns were observed in right versus left FL youth. Right FL participants showed increased left hippocampal and thalamic volume relative to left FL participants; whereas, the latter group showed increased right thalamic volume. DTI findings also indicated right FL children show greater MD of right fornix than other groups, whereas, left FL youth showed greater MD of left fornix. Right FL youth also showed lower FA of right fornix than left FL children, whereby the latter showed greater FA of left fornix and ATR. Differential associations between DTI indices and auditory/visual emotion-perception were observed across FL groups. Findings indicate diverging brain-behavioral relationships for emotion-perception among right and left FL children.

The face as an element of diversity. The ugliness of a face or a body and deformities were considered in 1800 as symbols of atavism, regression to being primates, or expression of inferior beings. The Italian physician Cesare Lombroso was the author of the concept of morphoanthropology, according to which the human being is judged on the basis of his or her physical connotations. The ugly person, with particular marks on his or her face and body, would be brought in as a criminal. Time has dissolved the value of Lombrosian theories, and scientific research has highlighted the influence of various factors in the genesis of crime. Genetic, biological, socioenvironmental factors, regulated by neurophysiology, which adds the effect of antagonism between the prefrontal cortex and the limbic cortex, explain the tendency to commit crime.

Although the thalamus is not considered primarily as a limbic structure, abundant evidence indicates the essential role of the thalamus as a modulator of limbic functions indirectly through the amygdala. The amygdala is a central component of the limbic system and serves an essential role in modulating the core processes including the memory, decision-making, and emotional reactions. The amygdalothalamic pathway is the largest direct amygdalo-diencephalic connection in the primates including the human brain. Given the crucial role of the amygdalothalamic tract (ATT) in memory function and diencephalic amnesia in stroke patients, diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of this pathway noninvasively. To date, few diffusion-weighted studies have focused on the amygdala, yet the fine neuronal connection of the amygdala and thalamus known as the ATT has yet to be elucidated. This study aimed to investigate the utility of high spatial resolution diffusion tensor tractography for mapping the trajectory of the ATT in the human brain. We studied 15 healthy right-handed human subjects (12 men and 3 women with age range of 24-37 years old). Using a high-resolution diffusion tensor tractography technique, for the first time, we were able to reconstruct and measure the trajectory of the ATT. We further revealed the close relationship of the ATT with the temporopontine tract and the fornix bilaterally in 15 healthy adult human brains., (© 2018 Wiley Periodicals, Inc.)

Decoding the chain from genes to cognition requires detailed insights how areas with specific gene activities and microanatomical architectures contribute to brain function and dysfunction. The Allen Human Brain Atlas contains regional gene expression data, while the JuBrain Atlas offers three-dimensional cytoarchitectonic maps reflecting interindividual variability. To date, an integrated framework that combines the analytical benefits of both scientific platforms towards a multi-level brain atlas of adult humans was not available. We have, therefore, developed JuGEx, a new method for integrating tissue transcriptome and cytoarchitectonic segregation. We investigated differential gene expression in two JuBrain areas of the frontal pole that we have structurally and functionally characterized in previous studies. Our results show a significant upregulation of MAOA and TAC1 in the medial area frontopolaris which is a node in the limbic-cortical network and known to be susceptible for gray matter loss and behavioral dysfunction in patients with depression. The MAOA gene encodes an enzyme which is involved in the catabolism of dopamine, norepinephrine, serotonin, and other monoaminergic neurotransmitters. The TAC1 locus generates hormones that play a role in neuron excitations and behavioral responses. Overall, JuGEx provides a new tool for the scientific community that empowers research from basic, cognitive and clinical neuroscience in brain regions and disease models with regard to gene expression.

Background: The limbic tracts are involved in crucial cerebral functions such as memory, emotion, and behavior. The complex architecture of the limbic circuit makes it harder to approach compared with other white matter networks. Our study aims to describe the 3-dimensional anatomy of the limbic white matter by the use of 2 complementary study methods, namely ex vivo fiber dissection and in vivo magnetic resonance imaging-based tractography., Methods: Three fiber dissection protocols were performed using blunt wooden instruments and a surgical microscope on formalin-fixed brains prepared according to the Klingler method. Diffusion tensor imaging acquisitions were done with a 3-Tesla magnetic resonance scanner on patients with head and neck pathology that did not involve the brain. Fiber tracking was performed with manually selected regions of interest., Results: Cingulum, fornix, the anterior thalamic peduncle, the accumbofrontal bundle, medial forebrain bundle, the uncinate fasciculus, the mammillothalamic tract, ansa peduncularis, and stria terminalis were dissected and fiber tracked. For each tract, location, configuration, segmentation, dimensions, dissection and tractography particularities, anatomical relations, and terminations are described. The limbic white matter tracts were systematized as 2 concentric rings around the thalamus. The inner ring is formed by fornix, mammillothalamic tract, ansa peduncularis, stria terminalis, accumbofrontal fasciculus, and medial forebrain bundle and anterior thalamic peduncle, and the outer ring is formed by the cingulum and uncinate fasciculus., Conclusions: This paper proposes a fiber-tracking protocol for the limbic tracts inspired and validated by fiber dissection findings that can be used routinely in the clinical practice., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The imperative role of white matter preservation in improving surgical functional outcomes is now recognized. Understanding the fundamental white matter framework is essential for translating the anatomic and functional literature into practical strategies for surgical planning and neuronavigation., Objective: To present a 3-dimensional (3-D) atlas of the structural and functional scaffolding of human white matter-ie, a "Surgical White Matter Chassis (SWMC)"-that can be used as an organizational tool in designing precise and individualized trajectory-based neurosurgical corridors., Methods: Preoperative diffusion tensor imaging magnetic resonance images were obtained prior to each of our last 100 awake subcortical resections, using a clinically available 3.0 Tesla system. Tractography was generated using a semiautomated deterministic global seeding algorithm. Tract data were conceptualized as a 3-D modular chassis based on the 3 major fiber types, organized along median and paramedian planes, with special attention to limbic and neocortical association tracts and their interconnections., Results: We discuss practical implementation of the SWMC concept, and highlight its use in planning select illustrative cases. Emphasis has been given to developing practical understanding of the arcuate fasciculus, uncinate fasciculus, and vertical rami of the superior longitudinal fasciculus, which are often-neglected fibers in surgical planning., Conclusion: A working knowledge of white matter anatomy, as embodied in the SWMC, is of paramount importance to the planning of parafascicular surgical trajectories, and can serve as a basis for developing reliable safe corridors, or modules, toward the goal of "zero-footprint" transsulcal access to the subcortical space.

Background: The developmental period of adolescence marks the initiation of new socioemotional and physical behaviors, including sexual intercourse. However, little is known about neurodevelopmental influences on adolescent sexual decision-making., Purpose: We sought to determine how subcortical brain volume correlated with condom use, and whether those associations differed by gender and pubertal development., Methods: We used FreeSurfer to extract subcortical volume among N = 169 sexually experienced youth (mean age 16.07 years; 31.95% female). We conducted multiple linear regressions to examine the relationship between frequency of condom use and subcortical volume, and whether these associations would be moderated by gender and pubertal development., Results: We found that the relationship between brain volume and condom use was better accounted for by pubertal development than by gender, and moderated the association between limbic brain volume and condom use. No significant relationships were observed in reward areas (e.g., nucleus accumbens) or prefrontal cortical control areas., Conclusions: These data highlight the potential relevance of subcortical socioemotional processing structures in adolescents' sexual decision-making.

Previous neuroimaging studies have highlighted the functional neural correlates of cardiac vagal activity, providing convergent evidence that the cardiac vagal function is controlled by a number of brain regions in the central autonomic network (CAN). However, it remains largely unknown whether the underlying anatomical basis of those identified regions are associated with individual difference in vagal function. To address the above issue, this study used a large sample of healthy subjects (n = 185) and voxel-based morphometry (VBM) analysis to verify brain morphometry associated with vagal control and the associations varied as a function of gender and age. Our results showed that high frequency component of heart rate variability (HF-HRV) was negatively correlated with grey matter volumes in the right putamen, caudate, amygdala, insula, superior temporal gyrus, temporal pole, and parahippocampal gyrus, demonstrating brain morphological variation in the right-sided striatal and limbic structures of the CAN associated with individual difference in cardiac vagal function. Additionally, gender and age effects on the relationship between cardiac vagal control and brain morphometry were not significant in the current dataset. These findings underscore the importance of striatal and limbic structures in parasympathetic control, and shed light on the underlying anatomical substrates of cardiac vagal activity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Changes in structural plasticity produced by the chronic exposure to drugs of abuse, such as alterations in dendritic spine densities, participate in the development of maladaptive learning processes leading to drug addiction. Understanding the neurobiological mechanisms involved in these aberrant changes is crucial to clarify the neurobiological substrate of addiction. Drug-induced locomotor sensitization has been widely accepted as a useful animal model to study these mechanisms related to drug addiction. We have evaluated the changes in structural plasticity in the mesocorticolimbic system involved in morphine-induced locomotor sensitization. The role of the cannabinoid receptor type 1 (CB1-R) in these neuroplastic alterations has also been studied using CB1-R-deficient (CB1-R KO) mice. Structural plasticity changes promoted by morphine are a highly dynamic phenomenon that evolves during the entire time course of the behavioral sensitization in wild-type (WT) animals. The different phases of the sensitization process were related to specific changes in connectivity between neurons revealed by modifications in dendritic spines in specific areas of the mesocorticolimbic system. Moreover, the lack of morphine-induced locomotor sensitization in CB1-R KO mice was accompanied by abnormal alterations in structural plasticity in the same mesocorticolimbic areas. These specific structural plasticity changes mediated by CB1-R activity seem necessary for the normal progression of morphine-induced locomotor sensitization and could play a critical role in the addictive process., (© 2015 Society for the Study of Addiction.)

The amygdala is known to have a role in core processes regulated by the limbic system such as motivation, memory, emotion, social behavior, self-awareness as well as certain primitive instincts. Several functional studies have investigated some of these brain tasks of the human limbic system. However, the underlying neuronal fiber connectivity of the amygdalo-diencephalon, as part of the limbic system, has not been delineated separately by prior diffusion-weighted imaging studies. The ability to trace the underlying fiber connections individually will be helpful in understanding the neurophysiology of these tracts in different functions. To date, few diffusion-weighted studies have focused on the amygdala, yet the fine connections of the amygdala, hypothalamus, septum or other adjacent limbic structures have yet to be elucidated by diffusion-weighted tractography studies. We therefore aimed to further investigate these fine neuronal connections using fiber tractography and high spatial resolution diffusion tensor imaging on 3T on 15 healthy right-handed male human subjects (age range 24-37 years). The ventral amygdalofugal pathway, anterior commissure and stria terminalis are the three main efferent pathways of the amygdala. We delineated the detailed trajectories of the ventral amygdalofugal tract, anterior commissure and their connections bilaterally in 15 normal adult human brains. Using a high-resolution diffusion tensor tractography technique, for the first time, we were able to demonstrate the trajectory of amygdalofugal tract and its connections to the hypothalamic and septal nuclei. We further revealed, for the first time, the close relationship of the amygdalofugal tract and anterior commissure with the fornix, stria terminalis and uncinate fasciculus bilaterally in 15 healthy adult human brains.

Individual differences in cognitive ability and social behaviour are influenced by the variability in the structure and function of the limbic system. A strong heritability of the limbic cortex has been previously reported, but little is known about how genetic factors influence specific limbic networks. We used diffusion tensor imaging tractography to investigate heritability of different limbic tracts in 52 monozygotic and 34 dizygotic healthy adult twins. We explored the connections that contribute to the activity of three distinct functional limbic networks, namely the dorsal cingulum ('medial default-mode network'), the ventral cingulum and the fornix ('hippocampal-diencephalic-retrosplenial network') and the uncinate fasciculus ('temporo-amygdala-orbitofrontal network'). Genetic and environmental variances were mapped for multiple tract-specific measures that reflect different aspects of the underlying anatomy. We report the highest heritability for the uncinate fasciculus, a tract that underpins emotion processing, semantic cognition, and social behaviour. High to moderate genetic and shared environmental effects were found for pathways important for social behaviour and memory, for example, fornix, dorsal and ventral cingulum. These findings indicate that within the limbic system inheritance of specific traits may rely on the anatomy of distinct networks and is higher for fronto-temporal pathways dedicated to complex social behaviour and emotional processing., (© The Author (2015). Published by Oxford University Press.)

Homeostatic adaptations to stress are regulated by interactions between the brainstem and regions of the forebrain, including limbic sites related to respiratory, autonomic, affective, and cognitive processing. Neuroanatomic connections between these homeostatic regions, however, have not been thoroughly identified in the human brain. In this study, we perform diffusion spectrum imaging tractography using the MGH-USC Connectome MRI scanner to visualize structural connections in the human brain linking autonomic and cardiorespiratory nuclei in the midbrain, pons, and medulla oblongata with forebrain sites critical to homeostatic control. Probabilistic tractography analyses in six healthy adults revealed connections between six brainstem nuclei and seven forebrain regions, several over long distances between the caudal medulla and cerebral cortex. The strongest evidence for brainstem-homeostatic forebrain connectivity in this study was between the brainstem midline raphe and the medial temporal lobe. The subiculum and amygdala were the sampled forebrain nodes with the most extensive brainstem connections. Within the human brainstem-homeostatic forebrain connectome, we observed that a lateral forebrain bundle, whose connectivity is distinct from that of rodents and nonhuman primates, is the primary conduit for connections between the brainstem and medial temporal lobe. This study supports the concept that interconnected brainstem and forebrain nodes form an integrated central homeostatic network (CHN) in the human brain. Our findings provide an initial foundation for elucidating the neuroanatomic basis of homeostasis in the normal human brain, as well as for mapping CHN disconnections in patients with disorders of homeostasis, including sudden and unexpected death, and epilepsy.

Paul Broca's concept of the "great limbic lobe" has had a huge impact on neuroscience. In this commentary, which accompanies the first English translation of the original paper, we comment on Broca's contribution and its influence on the understanding of the brain bases of emotion., (© 2015 Wiley Periodicals, Inc.)

Background: The mesial temporal region (MTR) comprises important components of the limbic system, as well as vital neurovascular structures. Because of its important functional role, as much healthy brain tissue as possible must be preserved while targeting resection of MTR lesions., Methods: A frontal minicraniotomy is used to access the MTR through a subfrontal approach. By opening the most medial part of the Sylvian fissure, the uncus-amygdala complex is exposed, and through this, the head of the hippocampus can be reached and removed as well., Conclusions: This approach is extremely suitable for MTR lesions, as it provides the advantage of sparing the most important functional structures of the temporal lobe, the temporal stem, and the limen insulae, as well as the optic radiations and the fronto-occipital connections.

Mechanisms underlying the profound parental effects on cognitive, emotional and social development in humans remain poorly understood. Studies with nonhuman models suggest variations in parental care affect the limbic system, influential to learning, autobiography and emotional regulation. In some research, nonoptimal care relates to decreases in neurogenesis, although other work suggests early-postnatal social adversity accelerates the maturation of limbic structures associated with emotional learning. We explored whether maternal sensitivity predicts human limbic system development and functional connectivity patterns in a small sample of human infants. When infants were 6 months of age, 20 mother-infant dyads attended a laboratory-based observational session and the infants underwent neuroimaging at the same age. After considering age at imaging, household income and postnatal maternal anxiety, regression analyses demonstrated significant indirect associations between maternal sensitivity and bilateral hippocampal volume at six months, with the majority of associations between sensitivity and the amygdala demonstrating similar indirect, but not significant results. Moreover, functional analyses revealed direct associations between maternal sensitivity and connectivity between the hippocampus and areas important for emotional regulation and socio-emotional functioning. Sensitivity additionally predicted indirect associations between limbic structures and regions related to autobiographical memory. Our volumetric results are consistent with research indicating accelerated limbic development in response to early social adversity, and in combination with our functional results, if replicated in a larger sample, may suggest that subtle, but important, variations in maternal care influence neuroanatomical trajectories important to future cognitive and emotional functioning.

Background: Images obtained through ultra-high-field 7.0-tesla magnetic resonance imaging with track-density imaging provide clear, high-resolution tractograms that have been hitherto unavailable, especially in deep brain areas such as the limbic and thalamic regions. This study is a largely pictorial description of the deep fiber tracts in the brain using track-density images obtained with 7.0-T diffusion-weighted imaging., Methods: To identify the fiber tracts, we selected 3 sets of tractograms and performed interaxis correlation between them. These tractograms offered an opportunity to extract new information in areas that have previously been difficult to examine using either in vivo or in vitro human brain tractography., Results: With this new technique, we identified 4 fiber tracts that have not previously been directly visualized in vivo: septum pellucidum tract, anterior thalamic radiation, superolateral medial forebrain bundle, and inferomedial forebrain bundle., Conclusions: We present the high-resolution images as a tool for researchers and clinicians working with neurodegenerative and psychiatric diseases, such as Parkinson disease, Alzheimer disease, and depression, in which the accurate positioning of deep brain stimulation is essential for precise targeting of nuclei and fiber tracts., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: The supplementary motor area (SMA) is frequently involved by brain tumours (particularly WHO grade II gliomas). Surgery in this area can be followed by the 'SMA syndrome', characterised by contralateral akinesia and mutism. Knowledge of the connections of the SMA can provide new insights on the genesis of the SMA syndrome, and a better understanding of the challenges related to operating in this region., Methods: White matter connections of the SMA were studied with both postmortem dissection and advance diffusion imaging tractography. Postmortem dissections were performed according to the Klingler technique. 12 specimens were fixed in 10% formalin and frozen at -15°C for 2 weeks. After thawing, dissection was performed with blunt dissectors. For diffusion tractography, high-resolution diffusion imaging datasets from 10 adult healthy controls from the Human Connectome Project database were used. Whole brain tractography was performed using a spherical deconvolution approach., Results: Five main connections were identified in both postmortem dissections and tractography reconstructions: (1) U-fibres running in the precentral sulcus, connecting the precentral gyrus and the SMA; (2) U-fibres running in the cingulate sulcus, connecting the SMA with the cingulate gyrus; (3) frontal 'aslant' fascicle, directly connecting the SMA with the pars opercularis of the inferior frontal gyrus; (4) medial fibres connecting the SMA with the striatum; and (5) SMA callosal fibres. Good concordance was observed between postmortem dissections and diffusion tractography., Conclusions: The SMA shows a wide range of white matter connections with motor, language and lymbic areas. Features of the SMA syndrome (akinesia and mutism) can be better understood on the basis of these findings., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: The purpose of the current study was to use diffusion tensor imaging (DTI) to conduct tractography of the optic radiations (OR) and its component bundles and to assess both the degree of hemispheric asymmetry and the inter-subject variability of Meyer's Loop (ML). We hypothesized that there are significant left versus right differences in the anterior extent of ML to the temporal pole (TP) in healthy subjects., Materials and Methods: DTI data were acquired on a 3T Siemens MRI system using a single-shot Spin Echo EPI sequence. The dorsal, central and ML bundles of the OR were tracked and visualized in forty hemispheres of twenty healthy volunteers. The uncinate fasciculus (UF) was also tracked in these subjects so that it could be used as a distinct anatomical reference. Measurements were derived for the distance between ML-TP, ML and the temporal horn (ML-TH) and ML and the uncinate fasciculus (ML-UF). Paired difference t-tests were carried out with SPSS 14.0., Results: ML and the UF were successfully tracked and visualized in all 20 volunteers. Significant hemispheric asymmetries were found for all measurements with left distances shorter than the right (P<0.005). In 50% of the subjects the left ML-UF distance was ≤1.9 mm., Conclusion: The results support our hypothesis and demonstrate that left ML-TP distances are significantly shorter than right ML-TP distances. These asymmetries are also reflected in shorter left distances between ML-TH and ML-UF. Moreover, these results are of interest to left-sided temporal lobe epilepsy surgery because it is not only more likely to disturb the anterior extent of ML but also renders the often closely located posterior aspect of the left UF more vulnerable to potential surgical impact., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

Background: Different strategies have been used to study the fiber tract anatomy of the human brain in vivo and ex vivo. Nevertheless, the ideal method to study white matter anatomy has yet to be determined because it should integrate information obtained from multiple sources., Objective: We developed an anatomic method in cadaveric specimens to study the central core of the cerebrum combining traditional white matter dissection with high-resolution 7-T magnetic resonance imaging (MRI) of the same specimen coregistered using a neuronavigation system., Methods: Ten cerebral hemispheres were prepared using the traditional Klingler technique. Before dissection, a structural ultrahigh magnetic field 7-T MRI study was performed on each hemisphere specifically prepared with surface fiducials for neuronavigation. The dissection was then performed from the medial hemispheric surface using the classic white fiber dissection technique. During each step of the dissection, the correlation between the anatomic findings and the 7-T MRI was evaluated with the neuronavigation system., Results: The anatomic study was divided in 2 stages: diencephalic and limbic. The diencephalic stage included epithalamic, thalamic, hypothalamic, and subthalamic components. The limbic stage consisted of extending the dissection to complete the Papez circuit. The detailed information given by the combination of both methods allowed us to identify and validate the position of fibers that may be difficult to appreciate and dissect (ie, the medial forebrain bundle)., Conclusion: The correlation of high-definition 7-T MRI and the white matter dissection technique with neuronavigation significantly improves the understanding of the structural connections in complex areas of the human cerebrum.

White matter development is important for efficient communication between brain regions, higher order cognitive functioning, and complex behaviors. Adolescents have a higher propensity for engaging in risky behaviors, yet few studies have explored associations between white matter integrity and risk taking directly. Altered white matter integrity in mid-adolescence was hypothesized to predict subsequent risk taking behaviors 1.5 years later. Adolescent substance users (predominantly alcohol and marijuana, n = 47) and demographically similar nonusers (n = 49) received diffusion tensor imaging at baseline (ages 16-19), and risk taking measures at both baseline and an 18-month follow-up (i.e., at ages 17-20). Brain regions of interest were the fornix, superior corona radiata, superior longitudinal fasciculus, and superior fronto-occipital fasciculus. In substance-using youth (n = 47), lower white matter integrity at baseline in the fornix and superior corona radiata predicted follow-up substance use (ΔR2 = 10-12%, ps < .01), and baseline fornix integrity predicted follow-up delinquent behaviors (ΔR2 = 10%, p < .01) 1.5 years later. Poorer fronto-limbic white matter integrity was linked to a greater propensity for future risk taking behaviors among youth who initiated heavy substance use by mid-adolescence. Most notable were relationships between projection and limbic-system fibers and future substance-use frequency. Subcortical white matter coherence, along with an imbalance between the maturation levels in cognitive control and reward systems, may disadvantage the resistance to engage in risk taking behaviors during adolescence., (2013 APA, all rights reserved)

The amygdaloid nuclei form an important hub of structures associated with diverse aspects of cognition and emotional behavior. Homologous structures have been determined in tetrapods, but homology of amygdala-like regions in bony fishes is presently unclear. Based on connectivity patterns, genoarchitecture, chemical neuroanatomy, and functional studies, we suggest that the dorsomedial portion of the pallium of Actinopterygii is the homolog of the basolateral/lateral amygdala ("frontotemporal amygdaloid system"), while the supracommissural and postcommissural portions of the subpallium are homologous to the extended central amygdala (central amygdaloid nucleus and bed nucleus of the stria terminalis). Nonetheless, the differentiation between these nuclei is not as clear-cut as in mammals, and there is no clear evidence for the existence of an "olfactory" medial amygdala in Actinopterygii, suggesting that the parcellation of one or two amygdaloid nuclei into many subnuclei occurred with the appearance of a true vomeronasal system., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Introduction: The basal ganglia (BG) have been implicated in different processes that control action such as the control of movement parameters but also in processing cognitive and emotional information from the environment. Here, we review existing anatomical data on the interaction between the BG and the limbic system that support implication of the BG in limbic functions., State of the Art: The BG form a system that is fairly different from the limbic system, but have strong ties, both anatomical and functional, to the latter. Different models have been proposed. In the parallel model, five segregated circuits from the frontal cortex are individualized and terminate in different regions of the BG and thalamus, before projecting back to their cortical area of origin. Based on the extrafrontal cortical projections, another model has been proposed. It subdivides the cortico-striatal projection into three functional territories: limbic, associative and sensorimotor. In a third spiral model, propagation is possible between limbic information processed by the most medial striatal neurons to motor information processed by the most lateral neurons., Perspectives: Three main levels of interaction between the BG system and the limbic system are considered. (1) The BG receive direct afferences from several structures associated with the limbic system. Limbic cortical areas project to the striatum, of which the internal architecture is particularly complex, with significant cross-species differences: a compartmental striosome/matrix subdivision described mainly in primates, and a core/shell topographic subdivision of the nucleus accumbens more sharply marked in rodents. (2) Projections from the amygdala form a patchy dorso-ventral progressive gradient in the nucleus accumbens and ventral caudate. (3) Both shell and striosomes receive limbic information from cortical and subcortical limbic structures and project to the dopaminergic neurons of the substantia nigra pars compacta, which in turn modulates their activity. (4) There is a significant overlap between the ventral portions of the BG, nucleus accumbens and ventral pallidum, and the ventral subcortical structures of the limbic system, extended amygdala and nucleus basalis., Conclusion: Important interactions exist between the limbic system and the BG system but questions remain about the role that this information plays in the functional organisation of this system. Is limbic information processed separately in the BG, or is it integrated to motor and cognitive information? Do pathological conditions such as obsessive-compulsive disorders or Tourette syndrome result from abnormal afferent limbic input to the BG or abnormal processing within the BG?, (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

In primates, prostriata is a small area located between the primary visual cortex (V1) and the hippocampal formation. Prostriata sends connections to multisensory and high-order association areas in the temporal, parietal, cingulate, orbitofrontal, and frontopolar cortices. It is characterized by a relatively simple histological organization, alluding to an early origin in mammalian evolution. Here we show that prostriata neurons in marmoset monkeys exhibit a unique combination of response properties, suggesting a new pathway for rapid distribution of visual information in parallel with the traditionally recognized dorsal and ventral streams. Whereas the location and known connections of prostriata suggest a high-level association area, its response properties are unexpectedly simple, resembling those found in early stages of the visual processing: neurons have robust, nonadapting responses to simple stimuli, with latencies comparable to those found in V1, and are broadly tuned to stimulus orientation and spatiotemporal frequency. However, their receptive fields are enormous and form a unique topographic map that emphasizes the far periphery of the visual field. These results suggest a specialized circuit through which stimuli in peripheral vision can bypass the elaborate hierarchy of extrastriate visual areas and rapidly elicit coordinated motor and cognitive responses across multiple brain systems., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To show the results of a device that generates automated olfactory stimuli suitable for functional magnetic resonance imaging (fMRI) experiments., Material and Methods: Ten normal volunteers, 5 women and 5 men, were studied. The system allows the programming of several sequences, providing the capability to synchronise the onset of odour presentation with acquisition by a trigger signal of the MRI scanner. The olfactometer is a device that allows selection of the odour, the event paradigm, the time of stimuli and the odour concentration. The paradigm used during fMRI scanning consisted of 15-s blocks. The odorant event took 2s with butanol, mint and coffee., Results: We observed olfactory activity in the olfactory bulb, entorhinal cortex (4%), amygdala (2.5%) and temporo-parietal cortex, especially in the areas related to emotional integration., Conclusions: The device has demonstrated its effectiveness in stimulating olfactory areas and its capacity to adapt to fMRI equipment., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

In mammals, empathy is crucial for living in social groups and caring for others. In this paper, we consider the structural and functional organization of empathy. We propose that empathy subsumes a variety of neurobiological processes and partially dissociable information processing subsystems, each of which has a unique evolutionary history. Even the most advanced and flexible forms of empathy in humans are built on more basic forms and remain connected to core subcortical and neurohormonal mechanisms associated with affective communication, parental care and social attachment processes. Considering empathy within a framework that recognizes both the continuities and the changes within a phylogenetic perspective provides a richer understanding of empathy and related neurobehavioral processes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Fiber dissection techniques were used to study the limbic system, in particular the Papez circuit. The course, length and anatomical relations of the structures that make up the Papez circuit were delineated. Ten previously frozen and formalin-fixed cadaveric human brains were used, and dissected according to the fiber dissection techniques of Klingler et al. (Schweiz Arch Neurol Psychiatry 1935;36:247-56). The primary dissection tools were thin and curved wooden and metallic spatulas with tips of varying sizes. We found that the Papez circuit (mean length: 350 mm) begins in the hippocampus and continues into the fornix to reach the mamillary body. From there, the mamillothalamic tract continues to the anterior nucleus of the thalamus, which in turn connects to the cingulum by means of anterior thalamic radiations (mean length: 30 mm). The cingulum courses around the corpus callosum to end in the entorhinal cortex, which then projects to the hippocampus, thus completing the circuit. The average length and breadth of the mamillothalamic tract was 18 mm and 1.73 mm respectively. The average length of the cingulum was 19.6 cm and that of the fornix was 71 mm. The entire circuit was anatomically dissected first in situ in the hemisphere and was then reconstructed outside after removing its various components using fine fiber dissection under a surgical microscope. We found that fiber dissection elegantly delineates the anatomical subtleties of the Papez circuit and provides a three-dimensional perspective of the limbic system. Intricate knowledge of the anatomy of this part of the brain aids the neurosurgeon while performing epilepsy surgery and while approaching intrinsic brain parenchymal, ventricular and paraventricular lesions., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Basic tendencies to detect and respond to significant events are present in the simplest single cell organisms and persist throughout all invertebrates and vertebrates. Within vertebrates, the overall brain plan is highly conserved, though differences in size and complexity also exist. The forebrain differs the most between mammals and other vertebrates. The classic notion that the evolution of mammals led to radical changes such that new forebrain structures (limbic system and neocortex) were added has not held up nor has the idea that so-called limbic areas are primarily involved in emotion. Modern efforts have focused on specific emotion systems, like the fear or defense system, rather than on the search for a general purpose emotion systems. Such studies have found that fear circuits are conserved in mammals, including humans. Animal work has been especially successful in determining how the brain detects and responds to danger. Caution should be exercised when attempting to discuss other aspects of emotion, namely subjective feelings, in animals since there are no scientific ways of verifying and measuring such states except in humans., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The present study elucidated whether early life stress alters the extracellular signal-regulated kinase (ERK) pathway that underlies fear retrieval and fear extinction based on a contextual fear conditioning paradigm, using a juvenile stress model. Levels of phospho-ERK (pERK), the active form of ERK, increased after fear retrieval in the hippocampal CA1 region but not in the medial prefrontal cortex (mPFC). ERK activation in the CA1 following fear retrieval was not observed in adult rats who received aversive footshock (FS) stimuli during the second postnatal period (2wFS), which exhibited low levels of freezing. In fear extinction, pERK levels in the CA1 were increased by repeated extinction trials, but they were not altered after extinction retrieval. In contrast, pERK levels in the mPFC did not change during extinction training, but were enhanced after extinction retrieval. These findings were compatible in part with electrophysiological data showing that synaptic transmission in the CA1 field and mPFC was enhanced during extinction training and extinction retrieval, respectively. ERK activation in the CA1 and mPFC associated with extinction processes did not occur in rats that received FS stimuli during the third postnatal period (3wFS), which exhibited sustained freezing behavior. The repressed ERK signaling and extinction deficit observed in the 3wFS group were ameliorated by treatment with the partial N-methyl-D-aspartate receptor agonist D-cycloserine. These findings suggest that early postnatal stress induced the downregulation of ERK signaling in distinct brain regions through region-specific regulation, which may lead to increased behavioral abnormalities or emotional vulnerabilities in adulthood., (© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

The knowledge that neonatal emotional experience and associated learning processes are critical in the maturation of prefronto-limbic circuits emphasizes the importance of preterm and neonatal care. The further improvement of care and intervention strategies requires a deeper understanding of epigenetic mechanisms mediating experience-induced synaptic reorganization underlying the emergence of emotional and cognitive behavioral traits. Interdisciplinary research efforts are needed in which pediatricians and developmental biologists and psychologists merge their knowledge, concepts, and methodology. The hope is that the translational relevance of research efforts can be improved through a greater interaction between basic and clinical scientists., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Normal circadian rhythms of behavior are disrupted in disorders involving the dopamine (DA) system, such as Parkinson's disease. We have reported previously using unilateral injections of the catecholamine toxin, 6-hydroxydopamine (6-OHDA), into the medial forebrain bundle that DA signaling regulates daily expression of the clock protein, PERIOD2 (PER2), in the dorsal striatum of the rat. In the present study, we made widespread lesions of DA fibers using large injections of 6-OHDA into the third ventricle to determine the involvement of DA in normal daily rhythms of wheel-running activity and PER2 patterns in the suprachiasmatic nucleus (SCN) and several regions of the limbic forebrain. Rats injected with 6-OHDA and housed in constant darkness were less active in the wheel and showed a disorganized pattern of activity in which wheel running was not confined to a specific phase over 24 h. The 6-OHDA injection had no effect on the daily PER2 pattern in the SCN, but blunted the normal rise in PER2 in the dorsal striatum. 6-OHDA also blunted PER2 expression in the periventricular nucleus of the hypothalamus, a region in which a daily PER2 pattern has not been previously reported in male rats, and in the oval nucleus of the bed nucleus of the stria terminalis, but not in the central nucleus of the amygdala. These results indicate that DA plays a prominent role in regulating circadian activity at both behavioral and molecular levels.

Chronic use of cocaine is associated with lasting alterations in brain metabolism, circuitry, and receptor properties. We used neuroimaging with pharmacological magnetic resonance imaging to assess alterations in response to cocaine (0.5 mg/kg) in animals trained to self-administer cocaine on a fixed-ratio 5 schedule of reinforcement, as well as saline-yoked controls, after 28 days of cocaine abstinence. We fitted the cerebral blood volume (CBV) curves for full-width half-maximum (FWHM) as well as peak CBV response. There were significant increases in the FWHM of the response curves in the cocaine self-administering (SA) animals as compared with saline-yoked controls in the medial prefrontal cortex (mPFC) and the caudate/putamen (CPu), and increases in peak CBV in the M1 motor cortex, CPu, and pedunculopontine tegmental nucleus. Functional connectivity analysis showed increased correlations in the cocaine SA rats upon acute cocaine challenge, especially in the S1, mPFC, and thalamus. As D3 receptor expression is postulated to increase following chronic cocaine administration, we also examined the response to 0.2 mg/kg of the D3-preferring agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT). Cocaine SA animals showed a decreased overall CBV response to this drug, except in the globus pallidus. The hypothalamus showed a negative CBV change in response to cocaine challenge, similar to that noted with the D3 agonist, and showed a smaller response in the cocaine SA animals than in the controls. Given the good coupling of cerebral hemodynamics with dopamine dynamics previously observed with pharmacological magnetic resonance imaging, these data suggest that increased persistence of dopamine in the prefrontal cortex may be responsible for some of the behavioral alterations observed subsequent to chronic cocaine use., (© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

Nesfatin-1 reduces food intake when injected centrally in rodents. We recently described wide distribution of nucleobindin2 (NUCB2)/nesfatin-1 immunoreactivity in rat brain autonomic nuclei activated by various stressors. We used C57BL/6 mice to localize brain NUCB2/nesfatin-1 immunoreactivity and assessed activation of NUCB2/nesfatin 1 neurons after water avoidance stress (WAS). Gastric emptying of a non-nutrient liquid was also determined. NUCB2/nesfatin-1 immunoreactivity was detected in cortical areas including piriform, insular, cingulate and somatomotor cortices, the limbic system including amygdaloid nuclei, hippocampus and septum, the basal ganglia, bed nucleus of the stria terminalis, the thalamus including paraventricular and parafascicular nuclei, the hypothalamus including supraoptic, periventricular, paraventricular (PVN), arcuate nuclei and ventromedial and lateral hypothalamic areas. Intensely labeled NUCB2/nesfatin-1 neurons were detected in a previously undefined region which we named intermediate dorsomedial hypothalamus. In the brainstem, NUCB2/nesfatin-1 immunoreactivity was detected in the raphe nuclei, Edinger-Westphal nucleus, locus coeruleus (LC), lateral parabrachial nucleus, ventrolateral medulla (VLM) and dorsal vagal complex. WAS induced Fos expression in 35% of NUCB2/nesfatin-1-immunoreactive neurons in the PVN, 50% in the LC, 54% in the rostral raphe pallidus, 58% in the VLM, 39% in the middle part of the nucleus of the solitary tract (NTS) and 33% in the caudal NTS. Nesfatin-1 injected intracerebroventricularly significantly decreased gastric emptying. These data showed that NUCB2/nesfatin-1 immunoreactivity is distributed in mouse brain areas involved in the regulation of stress response and visceral functions activated by an acute psychological stressor suggesting that nesfatin-1 might play a role in the efferent component of the stress response., (Published by Elsevier B.V.)