Lateral Nucleus Research Articles

Amygdala Nuclei Atrophy in Cognitive Impairment and Dementia: Insights from High-Resolution Magnetic Resonance Imaging

Background and Objectives: Cognitive impairment affects memory, reasoning, and problem-solving, with early detection being critical for effective management. The amygdala, a key structure in emotional processing and memory, may play a pivotal role in detecting cognitive decline. This study examines differences in amygdala nuclei volumes in patients with varying levels of cognitive performance to evaluate its potential as a biomarker. Material and methods: This cross-sectional study of 35 participants was conducted and classified into three groups: the normal (≥26), moderate (15–25), and low (≤14) cognitive performance groups based on the Montreal Cognitive Assessment (MoCA) scores. High-resolution magnetic resonance imaging at 3.0 T scanner was used to assess amygdala nuclei volumes. Results: Significant amygdala atrophy was observed in multiple amygdala nuclei across cognitive performance groups, with more pronounced changes in the low-performance group. The right hemisphere nuclei, including the lateral and basal nuclei, showed more significant differences, indicating their sensitivity to cognitive decline. Conclusions: This study highlights the potential of amygdala nuclei atrophy as a biomarker for cognitive impairment. Additional research with larger sample sizes and longitudinal designs is needed to confirm these findings and determine their diagnostic value.

Basal forebrain innervation of the amygdala: an anatomical and computational exploration

Theta oscillations of the mammalian amygdala are associated with processing, encoding and retrieval of aversive memories. In the hippocampus, the power of the network theta oscillation is modulated by basal forebrain (BF) GABAergic projections. Here, we combine anatomical and computational approaches to investigate if similar BF projections to the amygdaloid complex provide an analogous modulation of local network activity. We used retrograde tracing with fluorescent immunohistochemistry to identify cholinergic and non-cholinergic parvalbumin- or calbindin-immunoreactive BF neuronal subgroups targeting the input (lateral and basolateral nuclei) and output (central nucleus and the central bed nucleus of the stria terminalis) regions of the amygdaloid complex. We observed a dense non-cholinergic, putative GABAergic projection from the ventral pallidum (VP) and the substantia innominata (SI) to the basolateral amygdala (BLA). The VP/SI axonal projections to the BLA were confirmed using viral anterograde tracing and transsynaptic labeling. We tested the potential function of this VP/SI-BLA pathway in a 1000-cell biophysically realistic network model, which incorporated principal neurons and three major interneuron groups of the BLA, together with extrinsic glutamatergic, cholinergic, and VP/SI GABAergic inputs. We observed in silico that theta-modulation of VP/SI GABAergic projections enhanced theta oscillations in the BLA via their selective innervation of the parvalbumin-expressing local interneurons. Ablation of parvalbumin-, but not somatostatin- or calretinin-expressing, interneurons reduced theta power in the BLA model. These results suggest that long-range BF GABAergic projections may modulate network activity at their target regions through the formation of a common interneuron-type and oscillatory phase-specific disinhibitory motif.

Sex Differences in Central Amygdala Glutamate Responses to Calcitonin Gene-Related Peptide.

Women are disproportionately affected by chronic pain compared with men. While societal and environmental factors contribute to this disparity, sex-based biological differences in the processing of pain are also believed to play significant roles. The central lateral nucleus of the amygdala (CeLC) is a key region for the emotional-affective dimension of pain, and a prime target for exploring sex differences in pain processing since a recent study demonstrated sex differences in CGRP actions in this region. Inputs to CeLC from the parabrachial nucleus (PB) play a causal role in aversive processing and release both glutamate and calcitonin gene-related peptide (CGRP). CGRP is thought to play a crucial role in chronic pain by potentiating glutamatergic signaling in CeLC. However, it is not known if this CGRP-mediated synaptic plasticity occurs similarly in males and females. Here, we tested the hypothesis that female CeLC neurons experience greater potentiation of glutamatergic signaling than males following endogenous CGRP exposure. Using trains of optical stimuli to evoke transient CGRP release from PB terminals in CeLC, we find that subsequent glutamatergic responses are preferentially potentiated in CeLC neurons from female mice. This potentiation was CGRP dependent and involved a postsynaptic mechanism. This sex difference in CGRP sensitivity may explain sex differences in affective pain processing.

An intra-brainstem circuitry for pain-induced inhibition of itch.

Pain and itch are unpleasant and distinct sensations that give rise to behaviors such as reflexive withdrawal and scratching in humans and mice. Interestingly, it has been observed that pain modulate itch through the neural circuits housed in the brain and spinal cord. However, we are yet to fully understand the identities of, and mechanisms by which specific neural circuits mediate pain-induced modulation of itch. Independent studies indicate that brainstem nuclei such as the lateral parabrachial nucleus (LPBN) and rostral ventromedial medulla (RVM) are important for the suppression of itch by noxious somatosensory stimuli. Here, using mouse and viral genetics, rabies tracing, chemogenetics, and calcium imaging, we show that the synaptic connections between LPBN and RVM plays an instrumental role in the interactions between pain and itch. Notably, we found that the LPBN neurons that express the gene encoding the substance P receptor, Tacr1 (LPBNTacr1), synapse onto Tacr1-expressing RVM neurons (RVMTacr1). The RVMTacr1 neurons were found to be nociceptive, sufficient for inhibiting itch, and necessary for pain-induced itch suppression. Moreover, through brain-wide anterograde and retrograde viral tracing studies, we found that the RVMTacr1 neurons are bidirectionally connected with LPBN, periaqueductal gray (PAG), and lateral hypothalamic area (LHA). Thus, together, our data indicate that the RVMTacr1 neurons integrate nociceptive information to mediate itch-induced scratching and can mediate the physiological effects of itch through their downstream targets.

Opioid-induced respiratory depression: clinical aspects and pathophysiology of the respiratory network effects.

Important insights and consensus remain lacking for risk prediction of opioid-induced respiratory depression (OIRD), reversal of respiratory depression (RD), the pathophysiology of OIRD, and which sites make the most significant contribution to its induction. The ventilatory response to inhaled carbon dioxide is the most sensitive biomarker of OIRD. To accurately predict respiratory depression (RD), a multivariant RD prospective trial using continuous capnograph and oximetry examining 5 independent variables: age ≥60, sex, opioid naivety, sleep disorders, and chronic heart failure (PRODIGY trial), was undertaken. Intermittent oximetry alone substantially underestimates the incidence of RD. Naloxone, with an elimination half-life of ~33 min (c.f. morphine 2-3 h; fentanyl and congeners only 5-15 min) has limitations for the to rescue of patients with severe OIRD. Buprenorphine is potentially valuable in patients being treated long-term since its high μ-receptor (MOR) affinity makes it difficult for an opioid of lower affinity (e.g., fentanyl) to displace it from the receptor. In the last decade, synthetic opioids e.g., fentanyl, its potent analogs such as carfentanil and the benzimidazole derivative nitazene 'superagonists' have contributed to the exponential growth in opioid deaths due to RD. The MOR, encoded by gene Oprm1, is widely expressed in the central and peripheral nervous systems including centers that modulate breathing. Opioids bind to the receptors, but consensus is lacking on which site(s) makes the most significant contribution to induction of OIRD. Both the preBötzinger complex (preBötC), the inspiratory rhythm generator, and Kölliker-Fuse nucleus (KFN), the respiratory modulator, contribute to RD but receptor binding is not restricted to a single site. Breathing is composed of three phases, inspiration, post-inspiration, and active expiration, each generated by distinct rhythm-generating networks: the preBötC, the post-inspiratory complex (PiCo), and the lateral parafacial nucleus (pF L), respectively. Somatostatin expressing mouse cells involved in breathing regulation are not involved in opioid-induced RD.

Brainwide mesoscale functional networks revealed by focal infrared neural stimulation of the amygdala

Abstract The primate amygdala serves to evaluate emotional content of sensory inputs and modulate emotional and social behaviors; it modulates cognitive, multisensory and autonomic circuits predominantly via the basal, lateral, and central nuclei, respectively. Recent evidence has suggested the mesoscale (millimeter-scale) nature of intra-amygdala functional organization. However, the connectivity patterns by which these mesoscale regions interact with brainwide networks remain unclear. Using Infrared Neural Stimulation of single mesoscale sites coupled with mapping in ultrahigh field 7T functional Magnetic Resonance Imaging (INS-fMRI), we have discovered that these mesoscale sites exert influence over a surprisingly extensive scope of the brain. Our findings strongly indicate that mesoscale sites within the amygdala modulate brainwide networks through a ‘one-to-many’ (integral) way. Meanwhile, these connections exhibit a point-to-point (focal) topography. Our work provides new insights into the functional architecture underlying emotional and social behavioral networks, thereby opening up possibilities for individualized modulation of psychological disorders.

Amygdala intercalated cells form an evolutionarily conserved system orchestrating brain networks.

The amygdala attributes valence and emotional salience to environmental stimuli and regulates how these stimuli affect behavior. Within the amygdala, a distinct class of evolutionarily conserved neurons form the intercalated cell (ITC) clusters, mainly located around the boundaries of the lateral and basal nuclei. Here, we review the anatomical, physiological and molecular characteristics of ITCs, and detail the organization of ITC clusters and their connectivity with one another and other brain regions. We describe how ITCs undergo experience-dependent plasticity and discuss emerging evidence demonstrating how ITCs are innervated and functionally regulated by neuromodulatory systems. We summarize recent findings showing that experience alters the balance of activity between different ITC clusters, thereby determining prevailing behavioral output. Finally, we propose a model in which ITCs form a key system for integrating divergent inputs and orchestrating brain-wide circuits to generate behavioral states attuned to current environmental circumstances and internal needs.

Reorganization of lateral habenula neuronal connectivity underlies pain-related impairment in spatial memory encoding.

Dysfunctional hyperactivity of the lateral habenula nucleus (LHb) has emerged as a critical marker for pain-related mood impairments. Acting as a central hub, the LHb filters and disseminates pertinent information to other brain structures during learning. However, it is not well understood how intra-LHb activity is altered during cognitive demand under neuropathic pain conditions. To address this gap, we implanted an optrode structure to record neuronal activity in adult male CD (rat strain without definition) rats during the execution of a delayed nonmatch-to-sample (DNMS) spatial working memory (WM) task. We selectively modulated intra-LHb network activity by optogenetically inhibiting local LHb CaMKIIα (calcium calmodulin-dependent protein kinase II alpha)-expressing neurons during the delay phase of the DNMS task. Behavioral assessments were conducted using a persistent rodent model of neuropathic pain-spared nerve injury. Our results showed that the induction of neuropathic pain disrupted WM encoding accuracy and intra-LHb functional neuronal connectivity. This disruption was reversed by optogenetic inhibition of LHb CaMKIIα-expressing neurons, which also produced antinociceptive effects. Together, our findings provide insight into how intra-LHb networks reorganize information to support different task contexts, suggesting that the abnormal pain-related intra-LHb dynamic segregation of information may contribute to poor cognitive accuracy in male rodents during pain experiences.

The hidden link: Investigating functional connectivity of rarely explored sub-regions of thalamus and superior temporal gyrus in Schizophrenia.

Functional magnetic resonance imaging (fMRI) stands as a pivotal tool in advancing our comprehension of Schizophrenia, offering insights into functional segregations and integrations. Previous investigations employing either task-based or resting-state fMRI primarily focused on large main regions of interest (ROI), revealing the thalamus and superior temporal gyrus (STG) as prominently affected areas. Recent studies, however, unveiled the cytoarchitectural intricacies within these regions, prompting a more nuanced exploration. In this study, resting-state fMRI was conducted on 72 schizophrenic patients and 74 healthy controls to discern whether distinct thalamic nuclei and STG sub-regions exhibit varied functional integrational connectivity to main networks and to identify the most affected sub-regions in Schizophrenia. Employing seed-based analysis, six sub-ROIs - four in the thalamus and two in the STG - were selected. Our findings unveiled heightened positive functional connectivity in Schizophrenic patients, particularly toward the anterior STG (aSTG) and posterior STG (pSTG). Notably, positive connectivity emerged between the medial division of mediodorsal thalamic nuclei (MDm) and the visual network, while increased functional connectivity linked the ventral lateral nucleus of the thalamus with aSTG. This accentuated functional connectivity potentially influences these sub-regions, contributing to dysfunctions and manifesting symptoms such as language and learning difficulties alongside hallucinations. This study underscores the importance of delineating sub-regional dynamics to enhance our understanding of the nuanced neural alterations in Schizophrenia, paving the way for more targeted interventions and therapeutic approaches.

Deep brain stimulation combined with morroniside promotes neural plasticity and motor functional recovery after ischemic stroke.

Until now, there has been an unmet need for treatments promoting chronic-phase post-stroke functional recovery. We previously found that morroniside promoted endogenous neurogenesis in ischemic stroke, but its therapeutic window was limited to the first 48h. Here, we aimed to explore whether deep brain stimulation (DBS) combined with morroniside could enhance neurogenesis in rats subjected to focal ischemic stroke and contributes to functional recovery. Beginning 2weeks after the endothelin-1-induced stroke, rats were administered DBS of lateral cerebellar nucleus consecutively for 14days, followed by morroniside for 7 consecutive days post-stimulation. Behavioral tests were used for assessing motor function. Local field potentials were recorded to evaluate neuronal excitability. Nissl staining was used to assess infarct volume. Immunofluorescence staining and Western blotting were carried out to uncover the stroke recovery mechanisms of DBS combined with morroniside treatment. The results showed that this combined treatment improved behavioral outcomes, enhanced cortical local field potentials, and diminished infarct volumes at 35days post-stroke. Moreover, it notably amplified neurogenic responses post-stroke, evidenced by the proliferation of BrdU/SOX2 and BrdU/DCX in the subventricular zone, and their subsequent differentiation into BrdU/NeuN and BrdU/VgulT1 in the ischemic penumbra. Moreover, the combined treatment also elevated the amount of BrdU/Olig2 and the level of axonal sprouting-related proteins in the perilesional cortex. Our results demonstrated that the combined treatment extended the neurorestorative efficacy of morroniside, reduced infarct size, enhanced neuronal excitability and accelerated sensorimotor function recovery. This therapeutic approach may emerge as a potential clinical intervention for chronic ischemic stroke.

Supraspinal Plasticity of Axonal Projections From the Motor Cortex After Spinal Cord Injury in Macaques.

During recovery following spinal cord injury in the macaque, the sensorimotor cortex on the same side as the injury (ipsilesional, unaffected) becomes activated and plays a role in guiding movements of the affected hand. Effective regulation of these movements by the ipsilesional sensorimotor cortex would depend not only on its ability to send motor commands directly to target muscles but also on coordinated functioning with higher-level motor planning systems such as the cortico-basal ganglia and cortico-cerebellar loops. In this study, using anterograde viral tracers, we analyzed the axonal trajectories of corticofugal fibers from the contralesional (affected) primary motor cortex (M1) at the brainstem level in two macaque monkeys with sub-hemisection spinal cord injury at the mid-cervical level. They showed considerable recovery of grasping movements after injury. We found an increase in axonal projections from the contralesional M1 to the contralateral putamen, ipsilateral lateral reticular nucleus, and contralateral pontine nucleus compared to projections from the ipsilesional (unaffected) M1. We propose that these increased projections from the contralesional M1 to the striatum and precerebellar nuclei on the nondominant side may function to recruit the ipsilesional M1 through the cortico-basal ganglia and cortico-cerebellar loops to control hand movements on the affected side during recovery.

Nesfatin-1 is involved in hyperbaric oxygen-mediated therapeutic effects in high fat diet-induced hyperphagia in mice.

Obesity is a worldwide health issue. Effective and safe methods for obesity management are highly desirable. In the current study, hyperbaric oxygen (HBO) treatment was investigated as a potential treatment against obesity-associated hyperphagia and hyperenergy intake. Diet induced obesity (DIO) mice model was established with high fat diet (HFD) feeding, HBO was then co-administered. Food and energy intake were assessed with nocturnal food intake assay. Immunohistochemistry for c-Fos was performed for neuronal activation in arcuate nucleus (ARC), paraventricular nucleus of hypothalamus (PVN) and lateral parabrachial nucleus (LPBN) of brain. Additionally, enzyme-linked immunosorbent assay (ELISA) in serum and immunofluorescence in LPBN were performed. Results indicated that HBO co-treatment effectively decreased food and energy intake in DIO mice, reverted the abnormal neuronal activation in the ARC and PVN, and enhanced both peripheral and central nesfatin-1 peptide levels without affecting serum leptin levels. While SHU9119 microinjection in LPBN effectively abolished the beneficial effects of HBO on body weight, visceral fat, nocturnal feeding and energy intake in DIO mice. In conclusion, HBO treatment could effectively protect against HFD-induced increase of food and energy intake, which is associated with its central effects against abnormal neuronal activation in ARC and PVN and enhanced peptide levels of nesfatin-1 both centrally and peripherally. The melanocortin system downstream of nesfatin-1 may exert a potential effect in this process.

Higher-order cortical and thalamic pathways shape visual processing streams in the mouse cortex.

Mammalian visual functions rely on distributed processing across interconnected cortical and subcortical regions. In higher-order visual areas (HVAs), visual features are processed in specialized streams that integrate feedforward and higher-order inputs from intracortical and thalamocortical pathways. However, the precise circuit organization responsible for HVA specialization remains unclear. We investigated the cellular architecture of primary visual cortex (V1) and higher-order visual pathways in the mouse, focusing on their roles in shaping visual representations. Using invivo functional imaging and neural circuit tracing, we found that HVAs preferentially receive inputs from both V1 and higher-order pathways tuned to similar spatiotemporal properties, with the strongest selectivity seen in layer 2/3 neurons. These neurons exhibit target-specific tuning and sublaminar specificity in their projections, reflecting cell-type-specific visual information flow. In contrast, HVA layer 5 pathways nonspecifically broadcast visual signals across cortical areas, suggesting a role in distributing HVA outputs. Additionally, thalamocortical pathways from the lateral posterior thalamic nucleus (LP) provide highly specific, nearly non-overlapping visual inputs to HVAs, complementing intracortical inputs and contributing to input functional diversity. Our findings suggest that the convergence of laminar and cell-type-specific pathways V1 and higher-order intracortical and thalamocortical pathways plays a key role in shaping the functional specialization and diversity of HVAs.

Gamma Knife Radiosurgery, central lateral thalamotomy and chronic neuropathic pain. A prospective single center study with long term follow-up

ObjectiveNeuropathic pain affects approximately 7-10% of the general population. Its risk tends to rise with age and can impact individuals of any gender. Managing neuropathic pain often requires a combination of strategies. Surgical treatment is considered for patients who fail medical therapy and develop chronic symptoms. The posterior part of the central lateral nucleus (CLp) represents a promising target for the treatment of these cases.We present our experience in using Gamma Knife Surgery (GKS) on the posterior part of the central lateral nucleus (CLp) for refractory neuropathic pain, examining its long-term efficacy and safety in patients with one of the longest pre-treatment pain duration in the literature. Furthermore, we examined certain factors that might influence the outcome of this technique. MethodsWe conducted a prospective study involving 9 patients who underwent GKS between 2020 and 2023.We employed Icon model Gamma Knife and Vantage model stereotactic frame. The planning process encompassed a dual localization system. The assessments involved the use of both the Visual Analogue Scale (VAS) and Barrow Neurological Institute (BNI) scales (6,12-month and then, annually). Data analysis was carried out using SPSS25. ResultsOur series consisted of 6 women and 3 men with an average age of 52.3±17.4 years.A maximum dose of 130 Gy was administered (eight bilateral, one unilateral).The mid-term postoperative period (1 year) showed that eight patients (88.9%)experienced significant pain relief (VAS p=0.011;BNI I-IIIa).The median follow-up time was 24.8±8.2 (12-37 months). At the last assessment, all patients maintained their improvement (VAS p=0.018;BNI I-II-IIIa/b).We found no association between patient age (p=0.329),duration of pre-treatment pain (p=0.469),multiple previous surgical treatments (p=0.750),or the pain's etiology (p=0.25),and poorer outcomes post CLp thalamotomy.None of the cases has experienced a recurrence so far.Both permanent morbidity and mortality were 0%. ConclusionsOur findings suggest that bilateral ablation of the CLp using GKS is both effective and safe for treating drug-resistant neuropathic pain.This simple,accurate and non-invasive surgical technique effectively achieves pain control across various localized areas and sustains a lasting clinical response,even in patients with multiple previous surgical interventions or prolonged pain duration. These findings encourage us to consider this technique as a highly beneficial strategy for these patients.

Lateral parabrachial nucleus: the commander-in-chief for nocifensive behavior expression in cold allodynia.

Lateral parabrachial nucleus: the commander-in-chief for nocifensive behavior expression in cold allodynia.

Machine learning diagnosis of schizophrenia using structural and functional images of the brain

Abstract. This study aims to provide earlier, and faster schizophrenia diagnosis based on neurocognitive, structural, and behavioral measures using machine learning. This is because current ways of diagnosis, while accurate, delay patients ability to seek medical care before observable, lasting symptoms develop and are prone to error and discrimination. To provide diagnosis, we used Linear Support Vector Machine (linear SVM), Random Forest (RF), Multilayer Perceptron (MLP), and k-Nearest Neighbor (kNN), all trained with neurocognitive and behavioral measures combined with either structural or functional MRI data or both of 99 subjects from the OpenNeuro public dataset. 100 iterations of classification were run, and results showed a higher-than-average accuracy for all classifiers using all combinations of parameters, with a highest accuracy of 0.75 using linear SVM trained with behavioral and neurocognitive measures and fMRI data. We found correlations between structural changes in AAL3 brain regions and n-back working memory task performance, noting that the inferior parietal gyrus, right precuneus, supplementary motor area, and the central lateral thalamic nucleus have the highest feature importance. This means that future studies can select these features for further clinical examination or for machine learning diagnosis. We conclude that linear SVM provides the highest average diagnostic accuracy, and that fMRI data often leads to more accurate algorithmic decisions than sMRI data and thus should be weighed more in future studies.

A vagus nerve dominant tetra-synaptic ascending pathway for gastric pain processing

Gastric pain has limited treatment options and the mechanisms within the central circuitry remain largely unclear. This study investigates the central circuitry in gastric pain induced by noxious gastric distension (GD) in mice. Here, we identified that the nucleus tractus solitarius (NTS) serves as the first-level center of gastric pain, primarily via the vagus nerve. The prelimbic cortex (PL) is engaged in the perception of gastric pain. The lateral parabrachial nucleus (LPB) and the paraventricular thalamic nucleus (PVT) are crucial regions for synaptic transmission from the NTS to the PL. The glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuitry is necessary and sufficient for the processing of gastric pain. Overall, our finding reveals a glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuitry that transmits gastric nociceptive signaling by the vagus nerve in mice. It provides an insight into the gastric pain ascending pathway and offers potential therapeutic targets for relieving visceral pain.

Sex differences in central amygdala glutamate responses to calcitonin gene-related peptide.

Women are disproportionately affected by chronic pain compared to men. While societal and environmental factors contribute to this disparity, sex-based biological differences in the processing of pain are also believed to play significant roles. The central lateral nucleus of the amygdala (CeLC) is a key region for the emotional-affective dimension of pain, and a prime target for exploring sex differences in pain processing since a recent study demonstrated sex differences in CGRP actions in this region. Inputs to CeLC from the parabrachial nucleus (PB) play a causal role in aversive processing, and release both glutamate and calcitonin gene-related peptide (CGRP). CGRP is thought to play a crucial role in chronic pain by potentiating glutamatergic signaling in CeLC. However, it is not known if this CGRP-mediated synaptic plasticity occurs similarly in males and females. Here, we tested the hypothesis that female CeLC neurons experience greater potentiation of glutamatergic signaling than males following endogenous CGRP exposure. Using trains of optical stimuli to evoke transient CGRP release from PB terminals in CeLC, we find that subsequent glutamatergic responses are preferentially potentiated in CeLC neurons from female mice. This potentiation was CGRP-dependent and involved a postsynaptic mechanism. This sex difference in CGRP sensitivity may explain sex differences in affective pain processing.

Aging-related NADPH diaphorase positive neurodegenerations in the sacral spinal cord of aged non-human primates

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) was used to detect neurodegenerations in aged monkeys. Our previous studies have shown that aging-related NADPH-d positive bodies (ANBs) and megaloneurites appeared in the lumbosacral spinal cord of aged rats and dogs, respectively. To determine the occurrence of megaloneurites and ANBs in non-human primates, we used NADPH-d histochemistry to perform an advanced study of aging-related alterations in aged male monkeys. We identified two distinct abnormal NADPH-d positive alterations, which were expressed as ANBs and megaloneurites, mainly distributed in the superficial dorsal horn, dorsal gray commissure, lateral collateral pathway (LCP) and sacral parasympathetic nucleus of the sacral spinal cord in aged monkeys. Meanwhile, large diameter punctate NADPH-d abnormalities occurred and scattered in the lateral white matter of the LCP and dorsal root entry zone at the same level of megaloneurites in the gray matter. Immunohistochemical results showed that megaloneurites and ANBs are two distinct abnormal alterations, with megaloneurites co-localizing with vasoactive intestinal peptide immunoreactivity, whereas ANBs were not co-localized. Both ANBs and megaloneurites provide consistent evidence that the anomalous NADPH-d alterations in the aged sacral spinal cord are referred to as a specialized aging marker in the pelvic visceral organs in non-human primates.

Multinuclear thalamic targeting with human stereotactic electroencephalography: surgical technique and nuances.

The authors recently demonstrated the utility of a novel multinuclear thalamic stereotactic electroencephalography (sEEG) approach to identify personalized seizure propagation networks through the human thalamus. In this study, they detail their strategy to efficiently sample the thalamus. The authors previously showed that a multilead orthogonal transsylvian approach allows lateral-medial sampling of bilateral anterior nuclei of the thalamus (ANTs), mediodorsal (MD) nuclei, and pulvinar (PLV) nuclei, with simultaneous capture of the opercular and insular regions. They also described a novel trans-massa intermedia trajectory to sample bilateral MD nuclei with a single electrode. For a second approach to multinuclear thalamic sampling, they designed a novel long-axis trajectory for posterior-to-anterior sampling of the lateral PLV nucleus, lateral MD nucleus, and ANT with a single electrode. Superficially, this trajectory samples from the posterior inferior temporal gyrus and then the posterior hippocampus, known as seizure network nodes. Concurrent with this long-axis trajectory, the centromedian nucleus can also be targeted with the orthogonal approach, minimizing the number of electrodes required to sample all 8 of the most relevant nuclei (4 on each side). The multinuclear thalamic sampling approaches resulted in no complications in a series of 34 patients. This study provides a strategy and specific implementation details for these approaches to identify the thalamic seizure networks that are increasingly important in the surgical treatment of epilepsy.