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In human and nonhuman primates, the amygdala paralaminar nucleus (PL) contains immature neurons. To explore the PL’s potential for cellular growth during development, we compared PL cells in 1) infant and adolescent macaques (control, maternally-reared), and in 2) infant macaques that experienced separation from their mother in the first month of life. In maternally-reared animals, the adolescent PL had fewer immature neurons, more mature neurons, and larger immature soma volumes compared to infant PL. There were also fewer total neurons (immature plus mature) in adolescent versus infant PL, suggesting that some neurons move out of the PL by adolescence. Maternal separation did not change mean immature or mature neuron counts in infant PL. However, across all infant animals, immature neuron soma volume was strongly correlated with mature neuron counts.tbr-1mRNA, a transcript required for glutamatergic neuron maturation, is significantly reduced in the maternally-separated infant PL (DeCampo et al, 2017), and was also positively correlated with mature neuron counts in infant PL. We conclude that immature neurons gradually mature by adolescence, and that the stress of maternal separation may shift this trajectory, as revealed by correlations between tbr1mRNA and mature neuron numbers across animals.

The ketogenic diet, a high-fat, low-carbohydrate therapy, has become an established treatment for pediatric epilepsy since 1921. There has recently been an increase in important studies on the ketogenic diet, and this review will highlight the most recent in order to provide a synthesis of where this field stands today.Clinical studies continue to support the use of ketogenic diets in epilepsy, with more recent trials supporting its use in adults. Clinical recommendations published in 2018 based on a decade of practice and research, guide implementation and management of the ketogenic diet in epilepsy. One of the most rapidly growing 'indications' includes the role of ketogenic diets in status epilepticus. An exciting new potential mechanism for how the ketogenic diet exerts its antiseizure effects is through changing the composition of the gut microbiome. Lastly, ketogenic diets are being applied to a range of neurological conditions from autism to Alzheimer's disease.The ketogenic diet is a versatile therapy, with growing clinical evidence and guidelines, widely used for the treatment of epilepsy. New indications include status epilepticus and neurological conditions other than epilepsy.

Prematurity is associated with significant neurological injury and impaired neurodevelopment. In neonatology, ultrasonography is frequently used to assess for neurological injury. Ultrasonography allows rapid bedside imaging without radiation. Its limitations include the need for operator experience, lack of quantification, and lower prognostic power when compared with magnetic resonance imaging. Elastography is one of several technical advances used to enhance the diagnostic capability of traditional ultrasound. By detecting differences in tissue stiffness between normal and abnormal tissue, elastography has the potential to add objective and quantitative data to ultrasound imaging. Quantitative values could then be used to help detect injury, correlate outcome to predict prognosis, and guide surgical intervention. Since developmental processes such as myelination and neuropil formation may also influence brain stiffness, elastography may also serve as a unique tool to further delineate developmental differences between preterm and term infants. In this review, we provide a general overview of elastography, its application in neonatal neuroimaging, and possible future directions.

The lateral division of the bed nucleus of the stria terminalis (BSTL) and central nucleus of the amygdala (Ce) form the two poles of the 'central extended amygdala', a theorized subcortical macrostructure important in threat-related processing. Our previous work in nonhuman primates, and humans, demonstrating strong resting fMRI connectivity between the Ce and BSTL regions, provides evidence for the integrated activity of these structures. To further understand the anatomical substrates that underlie this coordinated function, and to investigate the integrity of the central extended amygdala early in life, we examined the intrinsic connectivity between the Ce and BSTL in non-human primates using ex vivo neuronal tract tracing, and in vivo diffusion-weighted imaging and resting fMRI techniques. The tracing studies revealed that BSTL receives strong input from Ce; however, the reciprocal pathway is less robust, implying that the primate Ce is a major modulator of BSTL function. The sublenticular extended amygdala (SLEAc) is strongly and reciprocally connected to both Ce and BSTL, potentially allowing the SLEAc to modulate information flow between the two structures. Longitudinal early-life structural imaging in a separate cohort of monkeys revealed that extended amygdala white matter pathways are in place as early as 3weeks of age. Interestingly, resting functional connectivity between Ce and BSTL regions increases in coherence from 3 to 7weeks of age. Taken together, these findings demonstrate a time period during which information flow between Ce and BSTL undergoes postnatal developmental changes likely via direct Ce→BSTL and/or Ce↔SLEAc↔BSTL projections.

The lateral bed nucleus of the stria terminalis (BSTL) is involved in mediating anxiety-related behaviors to sustained aversive stimuli. The BSTL forms part of the central extended amygdala, a continuum composed of the BSTL, the amygdala central nucleus, and cell columns running between the two. The central subdivision (BSTLcn) and the juxtacapsular subdivision (BSTLJ) are two BSTL regions that lie above the anterior commissure, near the ventral striatum. The amygdala, a heterogeneous structure that encodes emotional salience, projects to both the BSTL and ventral striatum. We placed small injections of retrograde tracers into the BSTL, focusing on the BSTLcn and BSTLJ, and analyzed the distribution of labeled cells in amygdala subregions. We compared this to the pattern of labeled cells following injections into the ventral striatum. All retrograde results were confirmed by anterograde studies. We found that the BSTLcn receives stronger amygdala inputs relative to the BSTLJ. Furthermore, the BSTLcn is defined by inputs from the corticoamygdaloid transition area and central nucleus, while the BSTLJ receives inputs mainly from the magnocellular accessory basal and basal nucleus. In the ventral striatum, the dorsomedial shell receives inputs that are similar, but not identical, to inputs to the BSTLcn. In contrast, amygdala projections to the ventral shell/core are similar to projections to the BSTLJ. These findings indicate that the BSTLcn and BSTLJ receive distinct amygdala afferent inputs and that the dorsomedial shell is a transition zone with the BSTLcn, while the ventral shell/core are transition zones with the BSTLJ.

The primate amygdala is composed of multiple subnuclei that play distinct roles in amygdala function. While some nuclei have been areas of focused investigation, others remain virtually unknown. One of the more obscure regions of the amygdala is the paralaminar nucleus (PL). The PL in humans and non-human primates is relatively expanded compared to lower species. Long considered to be part of the basal nucleus, the PL has several interesting features that make it unique. These features include a dense concentration of small cells, high concentrations of receptors for corticotropin releasing hormone and benzodiazepines, and dense innervation of serotonergic fibers. More recently, high concentrations of immature-appearing cells have been noted in the primate PL, suggesting special mechanisms of neural plasticity. Following a brief overview of amygdala structure and function, this review will provide an introduction to the history, embryology, anatomical connectivity, immunohistochemical and cytoarchitectural properties of the PL. Our conclusion based on the following information, is that the PL is a unique subregion of the amygdala that may yield important clues about the normal growth and function of the amygdala, particularly in higher species.

Elucidation of the ‘fear circuit’ has opened exciting avenues for understanding and treating human anxiety disorders. However, the translation of rodent to human studies, and vice versa, depends on understanding the homology in relevant circuits across species. Although abundant evidence indicates that the hippocampal-amygdala circuit mediates contextual fear learning, previous studies indicate that this pathway is more restricted in the primate than in rodent. Moreover, cellular components of the amygdala differ across species. The paralaminar nucleus (PL) of the amygdala, a structure that is closely associated with the basal nucleus, is one example, having no clear homologue in rodents. In both human and nonhuman primates, the PL contains a subpopulation of immature-appearing neurons, which merge into the corticoamygdaloid transition area (CTA). To understand whether immature-appearing neurons are positioned to participate in fear circuitry, we first mapped the hippocampal-amygdala projection in the monkey. We then determined whether immature appearing neurons were targets of this path. Retrograde results show that the hippocampal inputs to the amygdala originate in uncal region (CA1’) and the rostral prosubiculum, consistent with earlier studies. The amygdalohippocampal area, ventral basal nucleus, the medial paralaminar nucleus, and its confluence with the CTA are the main targets of this projection. Immature neurons are prominent in the PL and corticoamygdaloid transition area (CTA), and are overlapped by anterogradely labeled fibers from CA1’, particularly in the medial PL and CTA. Hippocampal inputs to the amygdala are more focused in higher primates compared to rodents, supporting previous anatomic studies and recent data from human functional imaging studies of contextual fear. At the cellular level, a hippocampal interaction with immature neurons in the amygdala suggests a novel substrate for cellular plasticity, with implications for mechanisms underlying contextual learning and emotional memory processes.