Ultrasound-guided retromammillary injections in dogs: a feasibility, descriptive and anatomical study.

OBJECTIVE: To evaluate the feasibility of an ultrasound-guided technique targeting the medial branches of the dorsal ramus of the spinal nerves (DRSN) by injecting a dye solution at the caudal aspect of the base of lumbar mammillary processes [i.e. the retromammillary (RM) space]. STUDY DESIGN: Feasibility, descriptive, anatomical study. ANIMALS: Eleven canine cadavers. METHODS: Using anatomical dissections, the relationship between the mammillary processes and the branches of the DRSN of the thoracolumbar and lumbar spine was studied in two cadavers. Subsequently, ultrasound-guided RM injections were administered in nine cadavers, randomly assigned to low volume (LV; 0.01 mL kg-1) of a dye solution at multiple points from L3 to L6 on one side, and high volume (HV; 0.4 mL kg-1) at a single L4 point on the contralateral side. Gross anatomical dissections were immediately performed after the injections. The RM injections were feasible if ultrasonographic landmarks were identifiable in at least 80% of cases, and 80% of LV injections showed medial branch staining. A one-sample binomial test was used for testing feasibility. RESULTS: The medial branches emerged shortly after the DRSN exited the intervertebral foramen and traveled towards the caudal aspect of the base of the mammillary process, which served as the target injection point. With LV, 36 out of 36 (100%) injected medial branches were stained, meeting the criteria of feasibility (p < 0.001). The median (range) number of stained medial branches per cadaver were 4 (4-4) and 2 (1-3), with LV and HV, respectively. Although no lateral branches were stained with LV, 1 (0-2) was stained with HV. Neither ventral branch staining nor epidural spread was noted in any cadaver. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasound-guided RM injections are feasible and allow for selective staining of the medial branch of the DRSN in canine cadavers at the lumbar spine.

Physiological characteristics of neurons in the mammillary bodies align with topographical organization of subicular inputs.

The mammillary bodies (MBOs), a group of hypothalamic nuclei, play a pivotal role in memory formation and spatial navigation. They receive extensive inputs from the hippocampus through the fornix, but the physiological significance of these connections remains poorly understood. Damage to the MBOs is associated with various forms of anterograde amnesia. However, information about the physiological characteristics of the MBO is limited, primarily due to the limited number of studies that have directly monitored MBO activity along with population patterns of its upstream partners. Employing large-scale silicon probe recording in mice, we characterize MBO activity and its interaction with the subiculum across various brain states. We find that MBO cells are highly diverse in their relationship to theta, ripple, and slow oscillations. Several of the physiological features are inherited by the topographically organized inputs to MBO cells. Our study provides insights into the functional organization of the MBOs.

Anatomy of mamillo-accessory foramen and prevalence of ossified mamillo-accessory ligament in lumbar vertebrae related to age.

PURPOSE: Ossification of the mamillo-accessory ligament (MAL) results in the formation of a mamillo-accessory foramen (MAF), which is associated with aging. The MAL tethers the medial branches of the lumbar dorsal rami to the lumbar vertebrae. A MAL ossified at the lumbar vertebrae can cause low back pain by compressing the medial branch of a dorsal ramus. Age ranges related to ossification of the MAL have not been reported in previous studies. The objective of the present study was to determine the prevalence of ossification of the MAL in the lumbar column and its relationship to aging, and to measure the newly formed MAF at each level of the lumbar vertebrae. METHODS: This study examined 935 dried lumbar vertebrae from 187 donors at Khon Kaen University, Thailand, consisting of 93 females and 94 males. The research focused on ossification patterns of the MAL, categorizing them into three patterns. RESULTS: We found that over 50% of ossified MAL occurred in the 30-45-year-old range and the frequency increased with age. The prevalence of ossified lumbar MAL was 72.73%, especially in L5 on the left side in females (76.92%). The width of the MAF did not differ significantly between the sexes, but it was greater on the left side (2.46 ± 1.08; n = 76) than the right (2.05 ± 0.95; n = 72) (p = 0.016). CONCLUSION: Ossification of the MAL into the MAF progresses with age, leading to low back pain from nerve compression. Physicians should be aware of the MAF during anesthesia block to treat low back pain.

Age dependent path integration deficit in 5xFAD mice.

Alzheimer's disease (AD) is a severe neurodegenerative disorder and the most common form of dementia in elderly individuals, characterized by memory deficits, cognitive decline, and neuropathology. The identification of preclinical markers for AD remains elusive. We employed an ultrasound-evoked spatial memory assay to investigate path integration (PI) in wild type C57BL/6 J and 5xFAD mice. We observed significant recruitment of the mammillary bodies (MB) and subiculum (Sub) - core regions of the Papez circuit during PI, as indicated by increased expression of the immediate early gene c-Fos in C57BL/6 J mice. In 5xFAD mice, amyloid-beta (Aß) vulnerability in the MB and Sub was evident at 3-months of age, preceding widespread pathology at 5-months of age. In parallel, we detected significant behavioral deficits in PI in the 5XFAD mice at 5- but not 3-months of age. Sex based analysis revealed a more profound deficit in males compared to females at 5-months of age. Our data suggest PI may be as an early indicator of AD, potentially associated with dysfunction within the Papez circuit.

Scanning electron microscope-based evaluation of eggshell quality.

The eggshell is the outermost covering of an egg that provides physical and chemical protection. It is a major source of calcium and minerals for the growing embryo during incubation. The egg industry suffers from a considerable economic loss due to poor eggshell quality. Therefore, developing an accurate and precise method of determining eggshell quality is crucial in improving eggshells in subsequent generations of breeding stock. Hence, this study aimed to develop a method to accurately and precisely determine 1) eggshell thickness using a scanning electron microscope (SEM) and 2) eggshell mineral components using an SEM-Energy Dispersive Spectrometry (EDS) system. Four types of table eggs (N = 48; 12 eggs/group): Cage-Free Organic from the US Mainland (CFO-M) and Hawaii (CFO-H), Caged Non-Organic from the US Mainland (CNO-M), and Hawaii (CNO-H) were sourced from the grocery store. Approximately 0.5 mm2 pieces of eggshells from the equator region of the egg were taken and processed for visualization under the SEM. Three distinct layers of eggshell were identified under SEM: the outermost cuticle, the middle palisade, and the innermost mammillary region. The results showed that CFO-H eggs have a greater eggshell thickness (380.43 ± 2.69 µm) and effective thickness (306.28 ± 4.15 µm). Similarly, the mammillary knob count was denser in CNO-H eggs (186 ± 23.02 knobs/0.5 mm2). Calcium (97.36 ± 0.17%) was the highest among minerals in lower palisades (LP). The magnesium concentration was lowest in the LP region, whereas the phosphorus concentration was highest in the upper palisades. Our study established a scientific method to assess the eggshell quality and biochemical characteristics of eggs through SEM and EDS. This method can be used as a marker for selecting superior parent stock to improve eggshell quality in subsequent generations of breeding stock.

Network Localization of Spontaneous Confabulation.

OBJECTIVE: Spontaneous confabulation is a symptom in which false memories are conveyed by the patient as true. The purpose of the study was to identify the neuroanatomical substrate of this complex symptom and evaluate the relationship to related symptoms, such as delusions and amnesia. METHODS: Twenty-five lesion locations associated with spontaneous confabulation were identified in a systematic literature search. The network of brain regions functionally connected to each lesion location was identified with a large connectome database (N=1,000) and compared with networks derived from lesions associated with nonspecific (i.e., variable) symptoms (N=135), delusions (N=32), or amnesia (N=53). RESULTS: Lesions associated with spontaneous confabulation occurred in multiple brain locations, but they were all part of a single functionally connected brain network. Specifically, 100% of lesions were connected to the mammillary bodies (familywise error rate [FWE]-corrected p<0.05). This connectivity was specific for lesions associated with confabulation compared with lesions associated with nonspecific symptoms or delusions (FWE-corrected p<0.05). Lesions associated with confabulation were more connected to the orbitofrontal cortex than those associated with amnesia (FWE-corrected p<0.05). CONCLUSIONS: Spontaneous confabulation maps to a common functionally connected brain network that partially overlaps, but is distinct from, networks associated with delusions or amnesia. These findings lend new insight into the neuroanatomical bases of spontaneous confabulation.

Osteolipoma of tubercinerium: An incidental finding in a patient with schizophrenia.

A 45-year-old male patient with clinically suspected schizophrenia was referred for an MRI brain to look for organicity. An incidental lesion was noted on the right side of the tubercinerium with suspicious findings of osteolipoma. T1 and T2 weighted sequences showed a hyper-intense lesion suggestive of fatty intensity or hemorrhage. A homogenous blooming artefact was seen on gradient imaging suggestive of a calcific/hemorrhagic element. The referring clinician was conveyed the findings asking about the need for further imaging by CT. The patient was started on antipsychotics for schizophrenia. One week later, a CT head was obtained, which showed a fatty density lesion with a smooth, peripheral rim of hyperdensity. The HU value matched rim calcification suggesting radiological diagnosis of osteolipoma. The patient was kept under close observation and no specific therapy was guided to this lesion. The patient was responding well to pharmacotherapy (in terms of control of symptoms) confirming osteolipoma as an incidental finding. This case report establishes the role of adequate imaging in subtle brain lesions which may mimic primary lesion-producing neurological symptoms. The importance of clinical judgment and follow-up in guiding suitable therapy is also highlighted.

Converging diencephalic and hippocampal supports for episodic memory.

To understand the neural basis of episodic memory it is necessary to appreciate the significance of the fornix. This pathway creates a direct link between those temporal lobe and medial diencephalic sites responsible for anterograde amnesia. A collaboration with Andrew Mayes made it possible to recruit and scan 38 patients with colloid cysts in the third ventricle, a condition associated with variable fornix damage. Complete fornix loss was seen in three patients, who suffered chronic long-term memory problems. Volumetric analyses involving all 38 patients then revealed a highly consistent relationship between mammillary body volume and the recall of episodic memory. That relationship was not seen for working memory or tests of recognition memory. Three different methods all supported a dissociation between recollective-based recognition (impaired) and familiarity-based recognition (spared). This dissociation helped to show how the mammillary body-anterior thalamic nuclei axis, as well as the hippocampus, is vital for episodic memory yet is not required for familiarity-based recognition. These findings set the scene for a reformulation of temporal lobe and diencephalic amnesia. In this revised model, these two regions converge on overlapping cortical areas, including retrosplenial cortex. The united actions of the hippocampal formation and the anterior thalamic nuclei on these cortical areas enable episodic memory encoding and consolidation, impacting on subsequent recall.

Do the mammillary bodies atrophy with aging? A magnetic resonance imaging study.

PURPOSE: This retrospective study aimed to explore age-related atrophy of the mammillary bodies (MBs) based on their temporal change using magnetic resonance imaging (MRI). MATERIALS AND METHODS: The study included 30 adult outpatients who presented to the hospital and were followed for more than 100 months with annual MRIs. The bi-ventricular width (BVW), third ventricle width (TVW), and bi-mammillary dimension (BMD) were measured on axial T2-weighted imaging and analyzed. RESULTS: The 30 patients comprised 1 in their 40s, 5 in their 50s, 6 in their 60s, 11 in their 70s, 5 in their 80s, and 2 in their 90s. The MBs were consistently detected with left-to-right symmetry. The mean BVW was 32 ± 2.2 mm on the initial (BVW1) and 32 ± 2.4 mm on the last (BVW2) MRI. The mean TVW was 7.0 ± 2.3 mm on the initial (TVW1) and 7.6 ± 2.7 mm on the last (TVW2) MRI. Furthermore, the mean BMD was 9.9 ± 1.3 mm on the initial (BMD1) and 10 ± 1.3 mm on the last (BMD2) MRI. Statistically, no age ranges had a large dimension for BVW1, BVW2, TVW1, TVW2, BMD1, or BMD2. Changes between TVW1 and TVW2 were significantly different in the patients in their 80s; changes between BMD1 and BMD2 were not different for any age range or between sexes. CONCLUSIONS: Aging alone does not seem to promote MB atrophy. In healthy brains, the MBs may be stationary structures throughout life.

Neurochemistry of the mammillary body.

The mammillary body (MB) is a component of the extended hippocampal system and many studies have shown that its functions are vital for mnemonic processes. Together with other subcortical structures, such as the anterior thalamic nuclei and tegmental nuclei of Gudden, the MB plays a crucial role in the processing of spatial and working memory, as well as navigation in rats. The aim of this paper is to review the distribution of various substances in the MB of the rat, with a description of their possible physiological roles. The following groups of substances are reviewed: (1) classical neurotransmitters (glutamate and other excitatory transmitters, gamma-aminobutyric acid, acetylcholine, serotonin, and dopamine), (2) neuropeptides (enkephalins, substance P, cocaine- and amphetamine-regulated transcript, neurotensin, neuropeptide Y, somatostatin, orexins, and galanin), and (3) other substances (calcium-binding proteins and calcium sensor proteins). This detailed description of the chemical parcellation may facilitate a better understanding of the MB functions and its complex relations with other structures of the extended hippocampal system.

Estimates of total neuron number show that neonatal ethanol causes immediate and lasting neuron loss in cortical and subcortical areas.

In neonatal brain development there is a period of normal apoptotic cell death that regulates adult neuron number. At approximately the same period, ethanol exposure can cause a dramatic spike in apoptotic cell death. While ethanol-induced apoptosis has been shown to reduce adult neuron number, questions remain about the regional selectivity of the ethanol effect, and whether the brain might have some capacity to overcome the initial neuron loss. The present study used stereological cell counting to compare cumulative neuron loss 8 h after postnatal day 7 (P7) ethanol treatment to that of animals left to mature to adulthood (P70). Across several brain regions we found that the reduction of total neuron number after 8 h was as large as that of adult animals. Comparison between regions revealed that some areas are more vulnerable, with neuron loss in the anterior thalamic nuclei > the medial septum/vertical diagonal band, dorsal subiculum, and dorsal lateral geniculate nucleus > the mammillary bodies and cingulate cortex > whole neocortex. In contrast to estimates of total neuron number, estimates of apoptotic cell number in Nissl-stained sections at 8 h after ethanol treatment provided a less reliable predictor of adult neuron loss. The findings show that ethanol-induced neonatal apoptosis often causes immediate neuron deficits that persist in adulthood, and furthermore suggests that the brain may have limited capacity to compensate for ethanol-induced neuron loss.

Korsakoff's Syndrome and Alzheimer's Disease-Commonalities and Specificities of Volumetric Brain Alterations within Papez Circuit.

Background: Alzheimer's disease (AD) and Korsakoff's syndrome (KS) are two major neurocognitive disorders characterized by amnesia but AD is degenerative while KS is not. The objective is to compare regional volume deficits within the Papez circuit in AD and KS, considering AD progression. Methods: 18 KS patients, 40 AD patients (20 with Moderate AD (MAD) matched on global cognitive deficits with KS patients and 20 with Severe AD (SAD)), and 70 healthy controls underwent structural MRI. Volumes of the hippocampi, thalami, cingulate gyri, mammillary bodies (MB) and mammillothalamic tracts (MTT) were extracted. Results: For the cingulate gyri, and anterior thalamic nuclei, all patient groups were affected compared to controls but did not differ between each other. Smaller volumes were observed in all patient groups compared to controls in the mediodorsal thalamic nuclei and MB, but these regions were more severely damaged in KS than AD. MTT volumes were damaged in KS only. Hippocampi were affected in all patient groups but more severely in the SAD than in the KS and MAD. Conclusions: There are commonalities in the pattern of volume deficits in KS and AD within the Papez circuit with the anterior thalamic nuclei, cingulate cortex and hippocampus (in MAD only) being damaged to the same extent. The specificity of KS relies on the alteration of the MTT and the severity of the MB shrinkage. Further comparative studies including other imaging modalities and a neuropsychological assessment are required.

Hidradenitis suppurativa presenting as mammillary fistula in a teenage girl.

Hidradenitis suppurativa (HS) is a common skin disease in children and young adults. In this report, we describe an unusual case of HS presenting as a mammillary fistula (MF) in a teenage female. A thorough dermatologic history and exam resulted in diagnosis of HS. Identifying the underlying disease is key to appropriate treatment of a relapsing MF in the setting of HS.

Clinical characteristics and risk factors for bilateral lateral geniculate body pathology: a systematic review of the literature.

BACKGROUND: Case presentation of acute onset bilateral painless vision loss caused by bilateral infarction of the lateral geniculate bodies (LGB) and a systematic review of the literature. METHODS: A descriptive case report is presented on a 17-year-old female diagnosed with acute pancreatitis who developed acute onset bilateral painless vision loss. A systematic literature review of cases with bilateral LGB lesions was conducted across three electronic databases (PubMed/PubMed Central/MEDLINE, Scopus, and ScienceDirect). The review was conducted in concordance with PRISMA guidelines and prospectively registered on PROSPERO (CRD42022362491). RESULTS: The reported 17-year-old female was found to have MRI findings consistent with bilateral hemorrhagic infarction of the LGB and Purtscher-like retinopathy. A systematic literature review of bilateral LGB infarction yielded 23 records for analysis. 19/23 (82.6%) of reported cases occurred in women. Bilateral vision loss was noted in all cases. The average reported age was 27 years old with a range from 2-50. Gastrointestinal pathology (e.g., pancreatitis, gastroenteritis) was present in 8/23 (34.7%) of cases. 8/23 (34.7%) cases had neuroimaging or pathological evidence of hemorrhagic transformation of the infarct. Most cases experienced partial recovery of visual loss; only one case (4.7%) had complete visual recovery. 9/23 (39.1%) cases were reported from the United States and 4/23 (17.3%) from India. CONCLUSIONS: Bilateral LGB lesion is a rare cause of vision loss, typically caused by systemic diseases and with female preponderance. Purported pathophysiology relates to increased vulnerability of the LGB to ischemic and metabolic stress.

Delineation of intermammillary relationships using magnetic resonance imaging.

PURPOSE: No study has investigated intermammillary relationships using neuroimaging modalities. This study aimed to explore them using magnetic resonance imaging (MRI). MATERIALS AND METHODS: We enrolled 72 patients who underwent conventional MRI examinations, followed by constructive interference steady-state sequence in the coronal plane. The intermammillary distances (IMDs) were measured at the uppermost level of the intermammillary gap (IMDupp) and the lowest level (IMDlow) of the mammillary bodies (MBs). RESULTS: MBs with varying morphologies were consistently delineated. The appearance of both MBs could be classified into four patterns based on the size and relative levels, with the symmetrical type being the most common. Intermammillary relationships exhibited five patterns. In 69%, the IMDupp was discernible and measured 0.7 ± 0.4 mm, while it was not discernible in 31% due to the presence of intermammillary connection and adhesion. The age distribution did not differ between populations with and without discernible IMDupp. The IMDlow was measured 4.4 ± 0.9 mm. Although the IMDlow was not significantly different between both sexes; it was longer in subjects in their 70s. CONCLUSIONS: Intermammillary relationships show variable morphologies with gaps formed between both MBs. The IMDlow may become more evident in association with age-related increase in the width of the third ventricle and atrophy of the MBs.

Hemosiderin Detection inside the Mammillary Bodies Using Quantitative Susceptibility Mapping on Patients with Wernicke-Korsakoff Syndrome.

Hemorrhage inside the mammillary bodies (MMBs) is known to be one of the findings of Wernicke encephalopathy. Brain MRI of two patients with Wernicke-Korsakoff syndrome (WKS) demonstrated high susceptibility values representing hemosiderin deposition in MMBs by using quantitative susceptibility mapping (QSM). QSM provided additional information of susceptibility values to susceptibility-weighted imaging in diagnosis of WKS.

Mammillary Body Atrophy in Temporal Lobe Epilepsy With Hippocampal Sclerosis.

BACKGROUND AND PURPOSE: We aimed to determine 1) the frequency of mammillary body (MB) atrophy in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS), 2) the clinical significance of MB atrophy, and 3) the association between MB atrophy and volume changes in other subcortical limbic structures. METHODS: We enrolled 69 patients with pathologically confirmed TLE with HS, who underwent a standard anterior temporal lobectomy, as well as 40 healthy controls. We used the FreeSurfer deep-learning tool of U-Net to obtain the volumes of the subcortical limbic structures, including the MB, hypothalamus, basal forebrain, septal nuclei, fornix, and nucleus accumbens. MB atrophy was considered to be present when the MB volume was decreased relative to the healthy controls. RESULTS: MB atrophy was present in 18 (26.1%) of the 69 patients with TLE and HS. Among the clinical characteristics, the mean age at seizure onset was higher (25.5 vs. 15.9 years, p=0.027) and the median duration of epilepsy was shorter (149 vs. 295 months, p=0.003) in patients with than without MB atrophy. The basal forebrain (0.0185% vs. 0.0221%, p=0.004) and septal nuclei (0.0062% vs. 0.0075%, p=0.003) in the ipsilateral hemisphere of HS were smaller in the patients with MB atrophy. CONCLUSIONS: We observed ipsilateral MB atrophy in about one-quarter of patients with TLE and HS. The severity of subcortical limbic structure abnormalities was greater in patients without MB atrophy. These findings suggest that MB atrophy in TLE with HS is not rare, but it has little clinical significance.

Time to retire the serial Papez circuit: Implications for space, memory, and attention.

After more than 80 years, Papez serial circuit remains a hugely influential concept, initially for emotion, but in more recent decades, for memory. Here, we show how this circuit is anatomically and mechanistically naïve as well as outdated. We argue that a new conceptualisation is necessitated by recent anatomical and functional findings that emphasize the more equal, working partnerships between the anterior thalamic nuclei and the hippocampal formation, along with their neocortical interactions in supporting, episodic memory. Furthermore, despite the importance of the anterior thalamic for mnemonic processing, there is growing evidence that these nuclei support multiple aspects of cognition, only some of which are directly associated with hippocampal function. By viewing the anterior thalamic nuclei as a multifunctional hub, a clearer picture emerges of extra-hippocampal regions supporting memory. The reformulation presented here underlines the need to retire Papez serially processing circuit.

Construction of complex memories via parallel distributed cortical-subcortical iterative integration.

The construction of complex engrams requires hippocampal-cortical interactions. These include both direct interactions and ones via often-overlooked subcortical loops. Here, we review the anatomical organization of a hierarchy of parallel 'Papez' loops through the hypothalamus that are homologous in mammals from rats to humans. These hypothalamic loops supplement direct hippocampal-cortical connections with iterative reprocessing paced by theta rhythmicity. We couple existing anatomy and lesion data with theory to propose that recirculation in these loops progressively enhances desired connections, while reducing interference from competing external goals and internal associations. This increases the signal-to-noise ratio in the distributed engrams (neocortical and cerebellar) necessary for complex learning and memory. The hypothalamic nodes provide key motivational input for engram enhancement during consolidation.

The morphogenesis of porcine femoral head mammillary processes: A structural mechanism of biomechanical stability.

The capital femoral physis is a growth plate located between the head of the femur and femoral neck, which forms a temporary joint where growth plate cartilage is converted to bone by endochondral ossification. The bone-cartilage-bone interface develops a unique radial pattern of interdigitating mammillary processes that interlock the femoral head with the metaphysis, increasing biomechanical stability. The arrangement of these mammillary processes may not be a random occurrence and likely serves to provide mechanical mechanisms to enhance biomechanical stability. In this study, we provide a qualitative and quantitative analysis of porcine femoral head mammillary processes and focus on the analysis of six key points of development: the epiphyseal tubercle, epiphyseal cupping, growth plate slope angles, expansion of the epiphyseal subchondral bone plate, epiphyseal elongation, and the emergence of smaller, radially arranged mammillary processes. We introduce a metric of surface roughness analysis to quantify mammillary processes and apply it to analyze the development of the observed radial pattern of peripheral mammillary processes from birth to adolescence. We hypothesized that these processes develop to form a radial pattern with some degree of periodicity beginning relatively early in development of the joint and increase in prominence with age and weight of the animal. These findings may have important implications in the early diagnosis and treatment of the hip disorder slipped capital femoral epiphysis (SCFE). Underdevelopment of femoral head mammillary processes may reduce joint stability and could be a risk factor in SCFE.