Functional Anatomy Research Articles

Functional anatomy of the orbit in strabismus surgery: Connective tissues, pulleys, and the modern surgical implications of the "arc of contact" paradigm.

Oculomotricity is a multidimensional domain characterised by a delicate interplay of anatomical structures and physiological processes. This manuscript meticulously dissects the nuances of this interplay, bringing to the fore the integral role of the extraocular muscles (EOMs) and their intricate relationship with the myriad orbital connective tissues as it harmoniously orchestrates binocular movements, ensuring synchronised and fluid visual tracking. Historically, the peripheral oculomotor apparatus was conceptualised as a rudimentary system predominantly driven by neural directives. While widely accepted, this perspective offered a limited view of the complexities inherent in ocular movement mechanics. The twentieth century heralded a paradigm shift in this understanding. With advances in anatomical research and imaging techniques, a much clearer picture of the gross anatomy of the EOMs emerged. This clarity challenged traditional viewpoints, suggesting that the inherent biomechanical properties of the EOMs, coupled with their associated tissue pulleys, play a pivotal role in dictating eye movement dynamics. Central to this revised understanding is the "arc of contact" paradigm. This concept delves deep into the mechanics of eye rotation, elucidating the significance of the point of contact between the EOMs and the eyeball. The arc of contact is not just a static anatomical feature; its length and orientation play a crucial role in determining the effective torque generated by a muscle, thereby influencing the amplitude and direction of eye rotation. The dynamic nature of this arc, influenced by the position and tension of the muscle pulleys, offers a more comprehensive model for understanding ocular kinematics. Previously overlooked in traditional models, muscle pulleys have now emerged as central players in the biomechanics of eye movement. These anatomical structures, formed by dense connective tissues, guide the paths of the EOMs, ensuring that their pulling angles remain optimal across a range of gaze directions. The non-linear paths resulting from these pulleys provide a more dynamic and intricate understanding of eye movement, challenging two-dimensional, linear models of orbital anatomy. The implications of these revelations extend beyond mere theoretical knowledge. The insights garnered from this research promise transformative potential in the realm of strabismus surgery. Recognising the pivotal role of muscle pulleys and the "arc of contact" paradigm allows for more precise surgical interventions, ensuring better post-operative outcomes and minimising the risk of complications. Surgical procedures that previously relied on basic mechanical principles now stand to benefit from a more nuanced understanding of the underlying anatomical and physiological dynamics. In conclusion, this manuscript serves as a testament to the ever-evolving nature of scientific knowledge. Challenging established norms and introducing fresh perspectives pave the way for more effective and informed clinical interventions in strabismus surgery.

The Neurobiology of Formal Thought Disorder.

The concept of Formal Thought Disorder (FTD) is an ambiguous and disputed one, even though it has endured as a core psychopathological construct in clinical Psychiatry. FTD can be summarized as a multidimensional construct, reflecting difficulties or idiosyncrasies in thinking, language, and communication in general and is usually subdivided into positive versus negative. In this article, we aim to explore the putative neurobiology of FTD, ranging from changes in neurotransmitter systems to alterations in the functional anatomy of the brain. We also discuss recent critiques of the operationalist view of FTD and how they might fit in its biological underpinnings. We conclude that FTD might be the observable phenotype of many distinct underlying alterations in different proportions.

Functional Anatomy of Urogenital Hiatus Closure: the Perineal Complex Triad Hypothesis.

Urogenital hiatus enlargement is a critical factor associated with prolapse and operative failure. This study of the perineal complex was performed to understand how interactions among its three structures: the levator ani, perineal membrane, and perineal body-united by the vaginal fascia-work to maintain urogenital hiatus closure. Magnetic resonance images from 30 healthy nulliparous women with 3D reconstruction of selected subjects were used to establish overall geometry. Connection points and lines of action were based on perineal dissection in 10 female cadavers (aged 22-86years), cross sections of 4 female cadavers (aged 14-35years), and histological sections (cadavers aged 16 and 21years). The perineal membrane originates laterally from the ventral two thirds of the ischiopubic rami and attaches medially to the perineal body and vaginal wall. The levator ani attaches to the perineal membrane's cranial surface, vaginal fascia, and the perineal body. The levator line of action in 3D reconstruction is oriented so that the levator pulls the medial perineal membrane cranio-ventrally. In cadavers, simulated levator contraction and relaxation along this vector changes the length of the membrane and the antero-posterior diameter of the urogenital hiatus. Loss of the connection of the left and right perineal membranes through the perineal body results in diastasis of the levator and a widened hiatus, as well as a downward rotation of the perineal membrane. Interconnections involving the levator ani muscles, perineal membrane, perineal body, and vaginal fascia form the perineal complex surrounding the urogenital hiatus in an arrangement that maintains hiatal closure.

Learning functional human anatomy with a new interactive three-dimensional digital tool.

Human anatomy requires understanding spatial relationships among anatomical structures and is often perceived as difficult to learn by students. To overcome this concern, several digital tools exist with some strengths and limitations among which the lack of interactivity especially for complex functional anatomy learning. In this way, a new interactive three-dimensional tool called Antepulsio was designed. Antepulsio was assessed by comparing three groups of first year kinesiology students to test whether it is likely to favor functional anatomy learning during three training sessions spread over a week. The experiment was conducted during a real academic course. Laterality judgment, 3D spatial abilities and working memory abilities from all participants were previously collected to create three homogeneous groups: the active group (n = 17, 17.76 ± 0.56 years) interacted with Antepulsio, the passive group (n = 18, 17.89 ± 0.83 years) watched videos of Antepulsio while the control group (n = 15, 18.07 ± 0.80 years) performed a neutral activity unrelated to anatomy. Anatomy knowledge was also assessed during pretest, posttest, and retention test (8 weeks after the posttest). The most significant outcome of this study revealed that in case of better working visual memory, the active group outperformed the passive group between pretest and retention test (p < 0.01). In other words, Antepulsio tool is efficient only for students with high visuospatial working memory. These selective benefits of Antepulsio are discussed in terms of cognitive load, training duration and the necessary period of familiarization with the tool.

Pathway-selective optogenetics reveals the functional anatomy of top-down attentional modulation in the macaque visual cortex.

Spatial attention represents a powerful top-down influence on sensory responses in primate visual cortical areas. The frontal eye field (FEF) has emerged as a key candidate area for the source of this modulation. However, it is unclear whether the FEF exerts its effects via its direct axonal projections to visual areas or indirectly through other brain areas and whether the FEF affects both the enhancement of attended and the suppression of unattended sensory responses. We used pathway-selective optogenetics in rhesus macaques performing a spatial attention task to inhibit the direct input from the FEF to area MT, an area along the dorsal visual pathway specialized for the processing of visual motion information. Our results show that the optogenetic inhibition of the FEF input specifically reduces attentional modulation in MT by about a third without affecting the neurons' sensory response component. We find that the direct FEF-to-MT pathway contributes to both the enhanced processing of target stimuli and the suppression of distractors. The FEF, thus, selectively modulates firing rates in visual area MT, and it does so via its direct axonal projections.

The Fulcrum of the Human Heart (Cardiac fulcrum)

Introduction: The functional anatomy of the myocardium allows envisioning that it initiates and ends at the origin of the great vessels. In our research, we have always considered that it should have a point of attachment to allow its helical rotation to fulfill the fundamental movements of shortening-torsion (systole) and lengthening-detorsion (suction), which once found, was called the cardiac fulcrum. Materials and methods: A total of 31 hearts, arising from the morgue and slaughterhouse were used: 17 corresponded to bovids and 14 were human. Anatomical and histological studies were performed. The heart was fixed in 10% buffered formalin. Hematoxylin-eosin, Masson’s trichrome staining technique, and 4-micron sections were used for the histological study, and 10 % formalin was used as a buffer. Results: The anatomical investigations have revealed that all the hearts (bovids and humans) have myocardial support whose histological structure in the analyzed specimens presents with an osseous or chondroid-tendinous character. In this structure, which we have called the cardiac fulcrum, are inserted the myocardial fibers at the origin and end of the band, which correspond to the continuous myocardium coiled as a helix. Conclusion: This description of the fulcrum would end the problem of lack of support of the myocardium to fulfill its function of suction/ejection.

Review of Structural and Functional Anatomy of Kidney in Ayurvedic Literature with Special Reference to Diseases of the Kidney

Description of organs and their treatment in Ayurvedic texts is very brief. In today’s world when the diseases of organs like kidneys, heart, liver, and brain etc., are becoming very common, Ayurvedic practitioners find these descriptions inadequate to treat patients with such diseases. An effort was made to assess whether critical analysis of references related to kidneys in classical Ayurvedic texts provide inputs to an Ayurvedic Practitioner to understand the pathogenesis of Chronic Kidney Disease (CKD). Tantrayukti based interpretation of references of kidneys in classical Ayurvedic texts establishes that kidneys were known to, and are elaborately described in Ayurveda, with their anatomical details such as embryological origin, name, number, relation with other abdominal organs, location etc. They are known by the name of Vrukka, which are the abdominal organs that are two in number and are described as Basti Marma (which includes the kidneys, ureter, and Bladder) for the purpose of diagnosis, prognosis, and treatment of all urine related diseases. Basti Marma is one of the three Maha Marmas i.e., most important vital organs of the body viz., Shiro (~brain), Hridaya (~heart) and Basti (~bladders). Vrukka (kidney) is formed from the nutritious part of Kapha, Meda and Rakta, gives the inputs to the practitioner to consider the metabolism of these factors in diagnosis and treatment of CKD. Physiology of formation of urine is also elaborately described in Ayurveda. The reference of Sushruta which discusses about Sahastrshaha Sukshma mukhani (~ thousands of minute openings invisible to naked eye) where urine is formed resembles the description of glomerular filtration. Formation and processing by Samaana, role of Jathar Agni, Dhatvagni and Bhutagni in formation of Mutra (~urine), storage and excretion at the level of Bladder, by Apaana is defined clearly, and this description is of immense value for practitioners. Relation of Basti Marma to Kleda (~body fluids) and its pathological connection with specific diseases is also evident. Understanding of various factors viz., Kleda (~body fluids), Marma (~vital organs), Prana (~life force), Oja (~vitality), Kalaa (~Internal membranes) Jathar Agni, Dhatvagni, Bhutagni etc., and their role in pathogenesis of CKD provides Vaidyas with inputs to devise the line of treatment of patients suffering from CKD, taking into consideration the individual condition of each patient.

Barbed stitch reposition pharyngoplasty as a surgical treatment for sleep apnea patients

&lt;b&gt;&lt;br&gt;Introduction:&lt;/b&gt; Surgical methods for obstructive sleep apnea syndrome play an increasingly important role. The development of surgical techniques makes the procedure less invasive, achieves better treatment results, and has a greater possibility of restoring the normal function of the upper airway. One of the sleep surgery for obstructive sleep apnea syndrome is pharyngoplasty. Barbed Stitch Reposition Pharyngoplasty is a relatively new surgical technique introduced in 2012.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Aim:&lt;/b&gt; Description of Barbed Stitch Reposition Pharyngoplasty, indications, and contraindications for this procedure as well as the risk of complications and a success rate.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Material and method:&lt;/b&gt; A literature review and own experience were conducted in the PubMed database, from 2012–2023, on the surgical technique, e.g. Barbed Stitch Reposition Pharyngoplasty.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Results:&lt;/b&gt; A significant decrease in apnea/hypopnea index and oxygen desaturation index as well as daily sleepiness is observed in the majority of patients who underwent Barbed Stitch Reposition Pharyngoplasty. All patients suffer from postoperative sore throats of varying intensity. The pain may last up to 2 weeks postoperatively. The most common complications reported by patients include odynophagia – 71%, swallowing disorders – 51%, and short-term feeling of a foreign body in the throat – 52% [1–3]. The postoperative surgical success rate ranged 65.4–93% of cases.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Conclusions:&lt;/b&gt; Barbed Stitch Reposition Pharyngoplasty is a relatively safe and effective method of surgical treatment for obstructive sleep apnea syndrome. The success of the procedure is enhanced by proper patient selection, surgical experience, and knowledge of functional upper airway anatomy.&lt;/br&gt;

[Pelvic floor reconstruction-update 2024: prolapse-associated symptoms and their treatment].

Pelvic organ prolapse (POP) and associated symptoms of urinary incontinence, fecal incontinence, obstructive micturition, defecation, and pain are frequent and awidespread disease with relevant reduction of quality of life and high costs. New insights into functional anatomy and pathophysiology of these pelvic floor dysfunctions let us recognize how ligamentous laxities/defects lead to these dysfunctions. Results of the PROpel study (ClinicalTrials.gov-Identifier: NCT00638235) are shown in which adetailed observation of symptoms (patient-related outcome measures) pre- and postoperatively was performed. Ligamentous vaginal repair of POP enables symptom cure in high percentages for urinary urge incontinence (up to 82%), nocturia (up to 92%), obstructive micturition (up to 87%), fecal incontinence (58-72%), obstructive defecation (71-84%), and pain (53-90%), if caused by POP. Women with POP‑Q stage2 have similar symptom frequencies as women with POP‑Q stage3-4, and also similar cure rates of their symptoms. If good anatomical prolapse repair (in responders) was achieved, the cure rates for obstructive micturition, urinary urgency incontinence, and nocturia were significantly higher than in those women with less effective surgical repair. In the future, pelvic floor surgery should have symptom cure as the primary objective and should lead to improved quality of life. The different, currently performed techniques for POP repair have to be investigated concerning this matter.

Bilateral and asymmetrical localization of language function identified by the superselective infusion of propofol in an epilepsy patient with a mild malformation of cortical development: illustrative case.

Atypical localization of language function can result in unexpected postsurgical deficits after cortical resection, but it is difficult to predict the risk in the presurgical evaluation. The authors experienced a rare case of the bilateral and independent existence of different components of language function identified by segmented evaluation of anatomical anterior and posterior language areas using the superselective infusion of propofol. A 32-year-old right-handed female presented with drug-resistant epilepsy. Comprehensive epilepsy evaluation suggested that the epileptic foci involved the whole left frontal lobe but provided less evidence of structural abnormality. To estimate the extent of functional deterioration likely to be caused by an extended left frontal lobectomy, the authors evaluated segmented cortical function in the ipsi- and contralateral hemispheres by the superselective infusion of propofol into the branches of the intracranial artery. The results revealed bilateral and asymmetrical localization of language function because the patient presented with different components of aphasia in each hemisphere. Based on the authors' assessment of her functional tolerance, an extended left frontal lobectomy was performed and resulted in neurological deficits within the anticipated range. An accurate understanding of the correlations between vascular and functional anatomy and the highly specific evaluation of language function provides more advanced presurgical assessment, allowing more tailored planning of cortical resection.

Cardiac structure, function and coronary anatomy 10 years after isolated contemporary adjuvant radiotherapy in breast cancer patients with low cardiovascular baseline risk.

The effects of isolated contemporary low-dose breast cancer (BC) radiotherapy (RT) on the heart remain poorly understood. To assess the long-term impacts of BC-RT on cardiac structure and function. 76 women (62 ± 7 years) without history of prior heart disease, who had undergone RT for either first left (n = 36) or right (n = 40) BC, without additional medical oncology therapy apart from hormonal treatment 11 ± 1 years earlier, underwent transthoracic echocardiography, cardiac MRI (CMR), Coronary CT (CTCA), NT-pro BNP, and a 6-minute walk test (6MWT). They were compared to 54 age-matched healthy female controls. By CTCA 68% of BC patients exhibited no or very mild coronary disease, while only 11% had moderate stenosis (50-69%) and 3% had significant stenosis (>70%). Despite slightly reduced regional echocardiographic midventricular strains, BC patients exhibited similar global left and right ventricular volumes, ejection fractions, and global strains by echocardiography and CMR as controls. Mitral E/e' ratios were slightly higher, and mitral deceleration times were slightly lower, but NT-proBNP was similar to controls. Also, 6MWT was normal. None had late gadolinium enhancement, and extracellular volume fraction was similar in BC (28 ± 3 vs 29 ± 3, p = 0.15) and controls. No differences were observed relative to dose or side of RT. Aside from minor alterations of regional strains and diastolic parameters, women who received isolated RT for BC had low prevalence of coronary disease, normal global systolic function, NT-pro BNP and exercise capacity and showed no structural changes by CMR, refuting significant long-term cardiotoxicity in such low-risk patients.

P.F. Lesgaft as the founder of the development of functional anatomy

This article presents new information about Petr Frantsevich Lesgaft, a scientist, anatomist, and physician who founded the development of functional anatomy and a scientifi cally based system of physical education in our country. 

Recent Advances in Imaging Macular Atrophy for Late-Stage Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. In late-stage AMD, geographic atrophy (GA) of dry AMD or choroidal neovascularization (CNV) of neovascular AMD eventually results in macular atrophy (MA), leading to significant visual loss. Despite the development of innovative therapies, there are currently no established effective treatments for MA. As a result, early detection of MA is critical in identifying later central macular involvement throughout time. Accurate and early diagnosis is achieved through a combination of clinical examination and imaging techniques. Our review of the literature depicts advances in retinal imaging to identify biomarkers of progression and risk factors for late AMD. Imaging methods like fundus photography; dye-based angiography; fundus autofluorescence (FAF); near-infrared reflectance (NIR); optical coherence tomography (OCT); and optical coherence tomography angiography (OCTA) can be used to detect and monitor the progression of retinal atrophy. These evolving diverse imaging modalities optimize detection of pathologic anatomy and measurement of visual function; they may also contribute to the understanding of underlying mechanistic pathways, particularly the underlying MA changes in late AMD.

Functional Cerebral Venous Anatomy: A Perspective on Venous Collaterals Part II, Infratentorial Venous System

Abstract The infratentorial veins are densely packed in a smaller space compared to the supratentorial veins and have many variations, such as disconnections and anastomoses. Knowledge of the functional venous anatomy of the posterior fossa is becoming increasingly important in neurointerventional procedures. The basic brainstem veins are longitudinal and transverse veins. The venous drainage of the brainstem and cerebellum follows 3 paths: superior (Galenic), anterior (petrosal), and posterior (torcular). Knowledge of the basic venous anatomy of the brainstem and cerebellum is essential for understanding the routes and patterns of venous drainage under pathological conditions, particularly in arteriovenous shunts. This review describes posterior fossa venous development and the functional venous anatomy of the posterior fossa, mainly the veins of the brainstem, cerebellum, and the emissary veins.

Functional Cerebral Venous Anatomy from the Viewpoint of Venous Collaterals Part I, Supratentorial Superficial and Deep Venous System

Abstract Supratentorial veins are divided into superficial and deep venous systems. Most superficial veins drain into the superior sagittal sinus, cavernous sinus, transverse sinus, and inferior sagittal sinuses. Most deep veins drain into the internal cerebral vein, and some drain into the basal vein of Rosenthal, which head toward the great cerebral vein of Galen. The functional anatomy of the supratentorial cerebral veins can be explained by dividing them into (1) veins on the lateral surface of the cerebral hemisphere, (2) the basal vein of Rosenthal system, and (3) the internal cerebral vein system. Many anastomotic channels exist between the superficial venous systems, veins at the base of the brain, and transcerebral veins. To understand and prevent adverse neurointerventional effects, in this study, we review the cerebral venous anatomy from the viewpoint of venous collaterals.

Rotitome-G: Principles and design concept of experimental compliant continuum robotic microsurgical endoscopic sarcotome for pixel/voxel-level target access neurosurgery

The practice of minimal access surgery is widely accepted, and it has become prevalent with improved endoscope design. The traditional microscope in neurosurgery is gradually being challenged by the neuro-endoscope for its direct co-axial vision and direct illumination of the deep set subcortical pathology. The conceptualized design of Rotitome-G is based on compliant continuum robotic system. The system is a biomimicry of muscular hydrostat anatomy of the elephant trunk, a plant tendril, and many similar structures in the animal world with an infinite degree of freedom. The article describes the functional anatomy of these structures and the extensor expansion of the human finger as applied to the construction and implementation of the Rotitome-G. This flexible microsurgical endoscope integral to its design has unique cutting tool versions and multiple assistive tools passed through single ‘target access’ burr hole aperture. It is navigable within the surgical space co-relative to the image space to increase precision and improve the volume of tumour resection. The current study is theoretical and further work is in progress to assess its surgical capabilities to bring it to the clinical arena.

Anatomy of the auditory cortex then and now.

Using neuroanatomical investigations in the macaque, Deepak Pandya and his colleagues have established the framework for auditory cortex organization, with subdivisions into core and belt areas. This has aided subsequent neurophysiological and imaging studies in monkeys and humans, and a nomenclature building on Pandya's work has also been adopted by the Human Connectome Project. The foundational work by Pandya and his colleagues is highlighted here in the context of subsequent and ongoing studies on the functional anatomy and physiology of auditory cortex in primates, including humans, and their relevance for understanding cognitive aspects of speech and language.

New Skeletons of the Ancient Dolphin Xenorophus sloanii and Xenorophus simplicidens sp. nov. (Mammalia, Cetacea) from the Oligocene of South Carolina and the Ontogeny, Functional Anatomy, Asymmetry, Pathology, and Evolution of the Earliest Odontoceti

The early diverging, dolphin-sized, cetacean clade Xenorophidae are a short-lived radiation of toothed whales (Odontoceti) that independently evolved two features long thought to be odontocete synapomorphies: the craniofacial and cochlear morphology underlying echolocation and retrograde cranial telescoping (i.e., posterior migration of the viscerocranium). This family was based on Xenorophus sloanii, which, for the past century, has been known only by a partial skull lacking a braincase and tympanoperiotics, collected around 1900 from the Ashley Formation (28–29 Ma, Rupelian) near Ladson, South Carolina. A large collection of new skulls and skeletons (ChM PV 5022, 7677; CCNHM 104, 168, 1077, 5995) from the Ashley Formation considerably expands the hypodigm for this species, now the best known of any stem odontocete and permitting evaluation of intraspecific variation and ontogenetic changes. This collection reveals that the holotype (USNM 11049) is a juvenile. Xenorophus sloanii is a relatively large odontocete (70–74 cm CBL; BZW = 29–31 cm; estimated body length 2.6–3 m) with a moderately long rostrum (RPI = 2.5), marked heterodonty, limited polydonty (13–14 teeth), prominent sagittal crest and intertemporal constriction, and drastically larger brain size than basilosaurid archaeocetes (EQ = 2.9). Dental morphology, thickened cementum, a dorsoventrally robust rostrum, and thick rugose enamel suggest raptorial feeding; oral pathology indicates traumatic tooth loss associated with mechanically risky predation attempts. Ontogenetic changes include increased palatal vomer exposure; fusion of the nasofrontal, occipito-parietal, and median frontal sutures; anterior lengthening of the nasals; elaboration of the nuchal crests; and blunting and thickening of the antorbital process. The consistent deviation of the rostrum 2–5° to the left and asymmetry of the palate, dentition, neurocranium, mandibles, and vertebrae in multiple specimens of Xenorophus sloanii suggest novel adaptations for directional hearing driven by the asymmetrically oriented pan bones of the mandibles. A second collection consisting of a skeleton and several skulls from the overlying Chandler Bridge Formation (24–23 Ma, Chattian) represents a new species, Xenorophus simplicidens n. sp., differing from Xenorophus sloanii in possessing shorter nasals, anteroposteriorly shorter supraorbital processes of the frontal, and teeth with fewer accessory cusps and less rugose enamel. Phylogenetic analysis supports monophyly of Xenorophus, with specimens of Xenorophus simplicidens nested within paraphyletic X. sloanii; in concert with stratigraphic data, these results support the interpretation of these species as part of an anagenetic lineage. New clade names are provided for the sister taxon to Xenorophidae (Ambyloccipita), and the odontocete clade excluding Xenorophidae, Ashleycetus, Mirocetus, and Simocetidae (Stegoceti). Analyses of tooth size, body size, temporal fossa length, orbit morphology, and the rostral proportion index, prompted by well-preserved remains of Xenorophus, provide insight into the early evolution of Odontoceti.

Functional Dissection of Ipsilateral and Contralateral Neural Activity Propagation Using Voltage-Sensitive Dye Imaging in Mouse Prefrontal Cortex.

Prefrontal cortex (PFC) intrahemispheric activity and the interhemispheric connection have a significant impact on neuropsychiatric disorder pathology. This study aimed to generate a functional map of FC intrahemispheric and interhemispheric connections. Functional dissection of mouse PFCs was performed using the voltage-sensitive dye (VSD) imaging method with high speed (1 ms/frame), high resolution (256 × 256 pixels), and a large field of view (∼10 mm). Acute serial 350 μm slices were prepared from the bregma covering the PFC and numbered 1-5 based on their distance from the bregma (i.e., 1.70, 1.34, 0.98, 0.62, and 0.26 mm) with reference to the Mouse Brain Atlas (Paxinos and Franklin, 2008). The neural response to electrical stimulation was measured at nine sites and then averaged, and a functional map of the propagation patterns was created. Intracortical propagation was observed in slices 3-5, encompassing the anterior cingulate cortex (ACC) and corpus callosum (CC). The activity reached area 33 of the ACC. Direct white matter stimulation activated area 33 in both hemispheres. Similar findings were obtained via DiI staining of the CC. Imaging analysis revealed directional biases in neural signals traveling within the ACC, whereby the signal transmission speed and probability varied based on the signal direction. Specifically, the spread of neural signals from cg2 to cg1 was stronger than that from cingulate cortex area 1(cg1) to cingulate cortex area 2(cg2), which has implications for interhemispheric functional connections. These findings highlight the importance of understanding the PFC functional anatomy in evaluating neuromodulators like serotonin and dopamine, as well as other factors related to neuropsychiatric diseases.

Cerebellar pathology in multiple sclerosis and experimental autoimmune encephalomyelitis: current status and future directions

Recent decades have witnessed significant progress in understanding mechanisms driving neurodegeneration and disease progression in multiple sclerosis (MS), but with a focus on the cerebrum. In contrast, there have been limited studies of cerebellar disease, despite the common occurrence of cerebellar symptoms in this disorder. These rare studies, however, highlight the early cerebellar involvement in disease development and an association between the early occurrence of cerebellar lesions and risk of worse prognosis. In parallel developments, it has become evident that far from being a region specialized in movement control, the cerebellum plays a crucial role in cognitive function, via circuitry connecting the cerebellum to association areas of the cerebrum. This complexity, coupled with challenges in imaging of the cerebellum have been major obstacles in the appreciation of the spatio-temporal evolution of cerebellar damage in MS and correlation with disability and progression. MS studies based on animal models have relied on an induced neuroinflammatory disease known as experimental autoimmune encephalomyelitis (EAE), in rodents and non-human primates (NHP). EAE has played a critical role in elucidating mechanisms underpinning tissue damage and been validated for the generation of proof-of-concept for cerebellar pathological processes relevant to MS. Additionally, rodent and NHP studies have formed the cornerstone of current knowledge of functional anatomy and cognitive processes. Here, we propose that improved insight into consequences of cerebellar damage in MS at the functional, cellular and molecular levels would be gained by more extensive characterization of EAE cerebellar pathology combined with the power of experimental paradigms in the field of cognition. Such combinatorial approaches would lead to improved potential for the development of MS sensitive markers and evaluation of candidate therapeutics.