Neuroanatomical correlates of peripersonal space: bridging the gap between perception, action, emotion and social cognition.

Peripersonal space (PPS) is a construct referring to the portion of space immediately surrounding our bodies, where most of the interactions between the subject and the environment, including other individuals, take place. Decades of animal and human neuroscience research have revealed that the brain holds a separate representation of this region of space: this distinct spatial representation has evolved to ensure proper relevance to stimuli that are close to the body and prompt an appropriate behavioral response. The neural underpinnings of such construct have been thoroughly investigated by different generations of studies involving anatomical and electrophysiological investigations in animal models, and, recently, neuroimaging experiments in human subjects. Here, we provide a comprehensive anatomical overview of the anatomical circuitry underlying PPS representation in the human brain. Gathering evidence from multiple areas of research, we identified cortical and subcortical regions that are involved in specific aspects of PPS encoding.We show how these regions are part of segregated, yet integrated functional networks within the brain, which are in turn involved in higher-order integration of information. This wide-scale circuitry accounts for the relevance of PPS encoding in multiple brain functions, including not only motor planning and visuospatial attention but also emotional and social cognitive aspects. A complete characterization of these circuits may clarify the derangements of PPS representation observed in different neurological and neuropsychiatric diseases.

Do patients with neurological disorders benefit from immersive virtual reality? A scoping review on the emerging use of the computer-assisted rehabilitation environment.

INTRODUCTION: Virtual reality (VR) is an advanced technology that creates simulated environments and conditions. By offering the possibility of combining motor, cognitive, and well-being in conjunction with the potential to manipulate multi-sensorial features in a safe environment, VR has emerged as a promising powerful rehabilitation tool. Among advanced VR systems, various authors have highlighted promising effects in the rehabilitation of the computer-assisted rehabilitation environment (CAREN - Motekforce Link; Amsterdam, The Netherlands). In our scoping review, we aimed to map the existing evidence on the use of CAREN in the rehabilitation of neurological patients. EVIDENCE ACQUISITION: This scoping review was conducted following the PRISMA guidelines. A search was carried out for all peer-reviewed articles published until June 30, 2023, using the following databases: PubMed, Embase, Cochrane Database, PeDro and Web of Science. The following terms have been used: ("Cognitive Rehabilitation" OR "Motor Rehabilitation" OR "CAREN" or "Computer-Assisted Rehabilitation Environment") AND ("Virtual Reality" OR "Rehab"). EVIDENCE SYNTHESIS: From the assessed studies, only seven met the inclusion criteria: 1) one study concerned cognitive rehabilitation in patients suffering from Parkinson's Disease (PD); 2) one was on the usability of CAREN in PD patients; 3) two studies related to the influence of emotional components to CAREN rehabilitation; 4) three studies were related to motor rehabilitation using CAREN, and involved individuals with PD, Multiple Sclerosis, TBI, respectively. Generally, the few assessed studies demonstrate that CAREN is a safe and potentially effective tool to treat different symptoms (including gait and vestibular disturbances, executive function, depressive mood, and anxiety) in patients with different neurological disorders. CONCLUSIONS: The reviewed literature indicated the potential use of CAREN in improving motor and cognitive skills with conflicting results on emotional aspects. However, since the data comes from few and small sample size studies, further research is needed to confirm the effectiveness of the tool in neurorehabilitation.

Screw Stress Distribution in a Clavicle Fracture with Plate Fixation: A Finite Element Analysis.

Clavicle midshaft fractures are mostly treated surgically by open internal reduction with a superior or anteroinferior plate and screws or by intramedullary nailing. Screw positioning plays a critical role in determining the stress distribution. There is a lack of data on the screw position and the appropriate number of cortices required for plate fixation. The aim of this study is to evaluate the mechanical behavior of an anterior plate implanted in a fractured bone subjected to 120° of lateral elevation compared to a healthy clavicle using numerical simulations. Contact forces and moments used were obtained from literature data and applied to the healthy and fractured finite element models. Stresses of about 9 MPa were found on the healthy clavicle, while values of about 15 MPa were calculated on the plate of the fractured one; these stress peaks were reached at about 30° and 70° of elevation when the stress shielding on the clavicle sums all the three components of the solicitation: compression, flexion, and torsion. The stress distribution in a clavicle fracture stabilized with plates and screws is influenced by several factors, including the plate's position and design, the type of screw, and the biomechanical forces applied during movements.

A case report of agoraphobia following right parietal lobe surgery: changes in functional and structural connectivities of the multimodal vestibular network.

Agoraphobia is a visuo-vestibular-spatial disorder that may involve dysfunction of the vestibular network, which includes the insular and limbic cortex. We sought to study the neural correlates of this disorder in an individual who developed agoraphobia after surgical removal of a high-grade glioma located in the right parietal lobe, by assessing pre- and post-surgery connectivities in the vestibular network. The patient underwent surgical resection of the glioma located within the right supramarginal gyrus. The resection interested also portions of the superior and inferior parietal lobe. Structural and functional connectivities were assessed through magnetic resonance imaging before and 5 and 7 months after surgery. Connectivity analyses focused on a network comprising 142 spherical regions of interest (4 mm radius) associated with the vestibular cortex: 77 in the left and 65 in the right hemisphere (excluding lesioned regions). Tractography for diffusion-weighted structural data and correlation between time series for functional resting-state data were calculated for each pair of regions in order to build weighted connectivity matrices. Graph theory was applied to assess post-surgery changes in network measures, such as strength, clustering coefficient, and local efficiency. Structural connectomes after surgery showed a decrease of strength in the preserved ventral portion of the supramarginal gyrus (PFcm) and in a high order visual motion area in the right middle temporal gyrus (37dl), and decrease of the clustering coefficient and of the local efficiency in several areas of the limbic, insular cortex, parietal and frontal cortex, indicating general disconnection of the vestibular network. Functional connectivity analysis showed both a decrease in connectivity metrics, mainly in high-order visual areas and in the parietal cortex, and an increase in connectivity metrics, mainly in the precuneus, parietal and frontal opercula, limbic, and insular cortex. This post-surgery reorganization of the vestibular network is compatible with altered processing of visuo-vestibular-spatial information, yielding agoraphobia symptoms. Specifically, post-surgical functional increases of clustering coefficient and local efficiency in the anterior insula and in the cingulate cortex might indicate a more predominant role of these areas within the vestibular network, which could be predictive of the fear and avoiding behavior characterizing agoraphobia.

Brown adipose tissue human biomarkers: Which one fits best? A narrative review.

Adipose tissue (AT) is an endocrine metabolically dynamic active tissue that plays a central role in the systemic energy balance and metabolic regulation. Brown AT represents approximately 1% of adult human AT, with an energy-burning function that uses fat to create heat. Brown AT activity was measured using 18F-fluorodeoxyglucose positron emission tomography/computed tomography. It has been shown that cold exposure could promote brown AT activation. However, many factors, such as aging and body mass index, may interfere with this activity. Many authors have discussed the role of factors specifically secreted by the AT in response to cold exposure. The aim of this review is to properly understand the effects of cold on AT and biomarkers and their possible application in rehabilitation medicine. A comprehensive literature review was performed to identify published studies regarding biomarkers of cold effects on Brown AT searching the following databases: PubMed, Science Direct, and Web of Science, from 2012 to 2022. After evaluation of the inclusion and exclusion criteria, 9 studies were included in this review. We reported the overall influence of cold exposure on brown AT activity, its related biomarkers, and metabolism, demonstrating that the therapeutic role of cold exposure needs to be better standardized. From our data, it is important to design proper clinical trials because most cold applied protocols lack a common and homogeneous methodology.

In vivo probabilistic atlas of white matter tracts of the human subthalamic area combining track density imaging and optimized diffusion tractography.

The human subthalamic area is a region of high anatomical complexity, tightly packed with tiny fiber bundles. Some of them, including the pallidothalamic, cerebello-thalamic, and mammillothalamic tracts, are relevant targets in functional neurosurgery for various brain diseases. Diffusion-weighted imaging-based tractography has been suggested as a useful tool to map white matter pathways in the human brain in vivo and non-invasively, though the reconstruction of these specific fiber bundles is challenging due to their small dimensions and complex anatomy. To the best of our knowledge, a population-based, in vivo probabilistic atlas of subthalamic white matter tracts is still missing. In the present work, we devised an optimized tractography protocol for reproducible reconstruction of the tracts of subthalamic area in a large data sample from the Human Connectome Project repository. First, we leveraged the super-resolution properties and high anatomical detail provided by short tracks track-density imaging (stTDI) to identify the white matter bundles of the subthalamic area on a group-level template. Tracts identification on the stTDI template was also aided by visualization of histological sections of human specimens. Then, we employed this anatomical information to drive tractography at the subject-level, optimizing tracking parameters to maximize between-subject and within-subject similarities as well as anatomical accuracy. Finally, we gathered subject level tracts reconstructed with optimized tractography into a large-scale, normative population atlas. We suggest that this atlas could be useful in both clinical anatomy and functional neurosurgery settings, to improve our understanding of the complex morphology of this important brain region.

White matter substrates of functional connectivity dynamics in the human brain.

The contribution of structural connectivity to functional connectivity dynamics is still far from being elucidated. Herein, we applied track-weighted dynamic functional connectivity (tw-dFC), a model integrating structural, functional, and dynamic connectivity, on high quality diffusion weighted imaging and resting-state fMRI data from two independent repositories. The tw-dFC maps were analyzed using independent component analysis, aiming at identifying spatially independent white matter components which support dynamic changes in functional connectivity. Each component consisted of a spatial map of white matter bundles that show consistent fluctuations in functional connectivity at their endpoints, and a time course representative of such functional activity. These components show high intra-subject, inter-subject, and inter-cohort reproducibility. We provided also converging evidence that functional information about white matter activity derived by this method can capture biologically meaningful features of brain connectivity organization, as well as predict higher-order cognitive performance.

Effects of diffusion signal modeling and segmentation approaches on subthalamic nucleus parcellation.

The subthalamic nucleus (STN) is commonly used as a surgical target for deep brain stimulation in movement disorders such as Parkinson's Disease. Tractography-derived connectivity-based parcellation (CBP) has been recently proposed as a suitable tool for non-invasive in vivo identification and pre-operative targeting of specific functional territories within the human STN. However, a well-established, accurate and reproducible protocol for STN parcellation is still lacking. The present work aims at testing the effects of different tractography-based approaches for the reconstruction of STN functional territories. We reconstructed functional territories of the STN on the high-quality dataset of 100 unrelated healthy subjects and on the test-retest dataset of the Human Connectome Project (HCP) repository. Connectivity-based parcellation was performed with a hypothesis-driven approach according to cortico-subthalamic connectivity, after dividing cortical areas into three groups: associative, limbic and sensorimotor. Four parcellation pipelines were compared, combining different signal modeling techniques (single-fiber vs multi-fiber) and different parcellation approaches (winner takes all parcellation vs fiber density thresholding). We tested these procedures on STN regions of interest obtained from three different, commonly employed, subcortical atlases. We evaluated the pipelines both in terms of between-subject similarity, assessed on the cohort of 100 unrelated healthy subjects, and of within-subject similarity, using a second cohort of 44 subjects with available test-retest data. We found that each parcellation provides converging results in terms of location of the identified parcels, but with significative variations in size and shape. All pipelines obtained very high within-subject similarity, with tensor-based approaches outperforming multi-fiber pipelines. On the other hand, higher between-subject similarity was found with multi-fiber signal modeling techniques combined with fiber density thresholding. We suggest that a fine-tuning of tractography-based parcellation may lead to higher reproducibility and aid the development of an optimized surgical targeting protocol.

Does cybersickness affect virtual reality training using the Computer Assisted Rehabilitation Environment (CAREN)? Preliminary results from a case-control study in Parkinson's disease.

INTRODUCTION AND OBJECTIVE: This pilot study aimed to evaluate whether and to what extent cybersickness (CS) may affect a rehabilitation program using the Computer-assisted Rehabilitation Environment (CAREN), a virtual reality (VR) computer-assisted device for clinical rehabilitation. METHODS: The study was carried out on 30 subjects, 15 patients with Parkinson's Disease (PD) and 15 healthy controls (HC), which underwent a set of four exergames programmed by our team for PD rehabilitation training. RESULTS: All participants completed the Motion Sickness Susceptibility Questionnaire Short-form (MSSQ) before the training and the Motion Symptoms Assessment Questionnaire (MSAQ) immediately after a single CAREN session. Overall, mean MSAQ scores remained low after the session, suggesting that the users did not experience severe discomfort. We found no significant difference in MSAQ scores between the two groups, while there was a statistically significant difference for the subsection of MSAQ regarding the peripheral symptoms (i.e. sweating, cold sweating, feeling warm), which were higher in HC. Moreover, the results highlighted some correlation between MSSQ and MSAQ. Gastrointestinal symptoms in PD, as well as MSSQ and sopite-related symptoms in HC, were also correlated with susceptibility to CS. CONCLUSIONS: As CS is rarely reported after CAREN, this and similar devices may be considered comfortable and safe for patients' rehabilitation involving VR training, including PD persons.

Striatal topographical organization: Bridging the gap between molecules, connectivity and behavior.

The striatum represents the major hub of the basal ganglia, receiving projections from the entire cerebral cortex and it is assumed to play a key role in a wide array of complex behavioral tasks. Despite being extensively investigated during the last decades, the topographical organization of the striatum is not well understood yet. Ongoing efforts in neuroscience are focused on analyzing striatal anatomy at different spatial scales, to understand how structure relates to function and how derangements of this organization are involved in various neuropsychiatric diseases. While being subdivided at the macroscale level into dorsal and ventral divisions, at a mesoscale level the striatum represents an anatomical continuum sharing the same cellular makeup. At the same time, it is now increasingly ascertained that different striatal compartments show subtle histochemical differences, and their neurons exhibit peculiar patterns of gene expression, supporting functional diversity across the whole basal ganglia circuitry. Such diversity is further supported by afferent connections which are heterogenous both anatomically, as they originate from distributed cortical areas and subcortical structures, and biochemically, as they involve a variety of neurotransmitters. Specifically, the cortico-striatal projection system is topographically organized delineating a functional organization which is maintained throughout the basal ganglia, subserving motor, cognitive and affective behavioral functions. While such functional heterogeneity has been firstly conceptualized as a tripartite organization, with sharply defined limbic, associative and sensorimotor territories within the striatum, it has been proposed that such territories are more likely to fade into one another, delineating a gradient-like organization along medio-lateral and ventro-dorsal axes. However, the molecular and cellular underpinnings of such organization are less understood, and their relations to behavior remains an open question, especially in humans. In this review we aimed at summarizing the available knowledge on striatal organization, especially focusing on how it links structure to function and its alterations in neuropsychiatric diseases. We examined studies conducted on different species, covering a wide array of different methodologies: from tract-tracing and immunohistochemistry to neuroimaging and transcriptomic experiments, aimed at bridging the gap between macroscopic and molecular levels.

Is intensive gait training feasible and effective at old age? A retrospective case-control study on the use of Lokomat Free-D in patients with chronic stroke.

BACKGROUND: In the last decade, the number of people over 60 has increased, leading to various healthcare problems. The aim of this retrospective study is to evaluate the effects of robotic rehabilitation in elderly patients as well as their perception of usability and adaptation to intensive robotic neurorehabilitation. METHODS: This is a retrospective case-control study. Eighty elderly stroke patients were included in the analysis using an electronic data retrieval system. The enrolled patients were divided into two groups: the experimental group (EG) underwent rehabilitation training with Lokomat FreeD, equipped with a VR screen, while the control group (CG) performed traditional rehabilitation training. The two groups matched for age, sex, education, brain injury, stroke interval. The rehabilitation protocol included a total of 40 training sessions. RESULTS: Both types of rehabilitation led to an improvement in the perceived level of disability (FIM) and in the performance in gait and balance (TT), highlighting a significant improvement especially in the EG. However, only in the EG, Lokomat training had induced an increase in the distance covered in 10 min (10 m walk test), and a significant improvement in mood (HRS-D). Moreover, Lokomat-FreeD was well tolerated by patients with high levels of usability. CONCLUSIONS: Our results suggest that elderly patients may benefit from high-intensity robotic neurorehabilitation using the Lokomat-Pro FreeD.

Ventral intermediate nucleus structural connectivity-derived segmentation: anatomical reliability and variability.

The Ventral intermediate nucleus (Vim) of thalamus is the most targeted structure for the treatment of drug-refractory tremors. Since methodological differences across existing studies are remarkable and no gold-standard pipeline is available, in this study, we tested different parcellation pipelines for tractography-derived putative Vim identification. Thalamic parcellation was performed on a high quality, multi-shell dataset and a downsampled, clinical-like dataset using two different diffusion signal modeling techniques and two different voxel classification criteria, thus implementing a total of four parcellation pipelines. The most reliable pipeline in terms of inter-subject variability has been picked and parcels putatively corresponding to motor thalamic nuclei have been selected by calculating similarity with a histology-based mask of Vim. Then, spatial relations with optimal stimulation points for the treatment of essential tremor have been quantified. Finally, effect of data quality and parcellation pipelines on a volumetric index of connectivity clusters has been assessed. We found that the pipeline characterized by higher-order signal modeling and threshold-based voxel classification criteria was the most reliable in terms of inter-subject variability regardless data quality. The maps putatively corresponding to Vim were those derived by precentral and dentate nucleus-thalamic connectivity. However, tractography-derived functional targets showed remarkable differences in shape and sizes when compared to a ground truth model based on histochemical staining on seriate sections of human brain. Thalamic voxels connected to contralateral dentate nucleus resulted to be the closest to literature-derived stimulation points for essential tremor but at the same time showing the most remarkable inter-subject variability. Finally, the volume of connectivity parcels resulted to be significantly influenced by data quality and parcellation pipelines. Hence, caution is warranted when performing thalamic connectivity-based segmentation for stereotactic targeting.

In Vivo Super-Resolution Track-Density Imaging for Thalamic Nuclei Identification.

The development of novel techniques for the in vivo, non-invasive visualization and identification of thalamic nuclei has represented a major challenge for human neuroimaging research in the last decades. Thalamic nuclei have important implications in various key aspects of brain physiology and many of them show selective alterations in various neurologic and psychiatric disorders. In addition, both surgical stimulation and ablation of specific thalamic nuclei have been proven to be useful for the treatment of different neuropsychiatric diseases. The present work aimed at describing a novel protocol for histologically guided delineation of thalamic nuclei based on short-tracks track-density imaging (stTDI), which is an advanced imaging technique exploiting high angular resolution diffusion tractography to obtain super-resolved white matter maps. We demonstrated that this approach can identify up to 13 distinct thalamic nuclei bilaterally with very high inter-subject (ICC: 0.996, 95% CI: 0.993-0.998) and inter-rater (ICC:0.981; 95% CI:0.963-0.989) reliability, and that both subject-based and group-level thalamic parcellation show a fair share of similarity to a recent standard-space histological thalamic atlas. Finally, we showed that stTDI-derived thalamic maps can be successfully employed to study structural and functional connectivity of the thalamus and may have potential implications both for basic and translational research, as well as for presurgical planning purposes.

Cerebellar Atrophy Associated with Primary Sjögren's Syndrome: Diagnosis, Therapy, and Virtual Reality Rehabilitation: A Case Report.

Cerebellar involvement in primary Sjögren's syndrome (pSS) is an uncommon condition, with only a limited number of cases described worldwide. A 43-year-old woman affected by cerebellar atrophy associated with pSS was referred to our center to undergo a cycle of physical rehabilitation therapy. Although motor symptoms started when the patient was 23 years of age, the underlying disease remained undiagnosed for several years. Neurological examination before rehabilitation revealed ataxic gait, dysmetria, nystagmus, and hypermetric saccades; the patients complained about unsteadiness while standing or walking. To improve balance and gait abilities, a 20-session cycle of balance rehabilitation, based on a combination of conventional physical therapy and virtual reality exergames, was prescribed. The outcomes of rehabilitation were evaluated with balance tests and three-dimensional (3D) gait analysis. To our knowledge, this is the first case describing the diagnostic workout for cerebellar atrophy associated with pSS and the subsequent motor rehabilitation. This work highlights the importance of early diagnosis and rehabilitation in patients with central nervous system involvement in pSS.

Robotic Rehabilitation in Spinal Cord Injury: A Pilot Study on End-Effectors and Neurophysiological Outcomes.

Robot-aided gait training (RAGT) has been implemented to provide patients with spinal cord injury (SCI) with a physiological limb activation during gait, cognitive engagement, and an appropriate stimulation of peripheral receptors, which are essential to entrain neuroplasticity mechanisms supporting functional recovery. We aimed at assessing whether RAGT by means of an end-effector device equipped with body weight support could improve functional ambulation in patients with subacute, motor incomplete SCI. In this pilot study, 15 patients were provided with six RAGT sessions per week for eight consecutive weeks. The outcome measures were muscle strength, ambulation, going upstairs, and disease burden. Furthermore, we estimated the activation patterns of lower limb muscles during RAGT by means of surface electromyography and the resting state networks' functional connectivity (RSN-FC) before and after RAGT. Patients achieved a clinically significant improvement in the clinical outcome measures substantially up to six months post-treatment. These data were paralleled by an improvement in the stair-climbing cycle and a potentiating of frequency-specific and area-specific RSN-FC patterns. Therefore, RAGT, by means of an end-effector device equipped with body weight support, is promising in improving gait in patients with subacute, motor incomplete SCI, and it could produce additive benefit for the neuromuscular reeducation to gait in SCI when combined with conventional physiotherapy.

Red nucleus structure and function: from anatomy to clinical neurosciences.

The red nucleus (RN) is a large subcortical structure located in the ventral midbrain. Although it originated as a primitive relay between the cerebellum and the spinal cord, during its phylogenesis the RN shows a progressive segregation between a magnocellular part, involved in the rubrospinal system, and a parvocellular part, involved in the olivocerebellar system. Despite exhibiting distinct evolutionary trajectories, these two regions are strictly tied together and play a prominent role in motor and non-motor behavior in different animal species. However, little is known about their function in the human brain. This lack of knowledge may have been conditioned both by the notable differences between human and non-human RN and by inherent difficulties in studying this structure directly in the human brain, leading to a general decrease of interest in the last decades. In the present review, we identify the crucial issues in the current knowledge and summarize the results of several decades of research about the RN, ranging from animal models to human diseases. Connecting the dots between morphology, experimental physiology and neuroimaging, we try to draw a comprehensive overview on RN functional anatomy and bridge the gap between basic and translational research.

Structural Connectivity-Based Parcellation of the Dopaminergic Midbrain in Healthy Subjects and Schizophrenic Patients.

Background and objectives: Functional deregulation of dopaminergic midbrain regions is a core feature of schizophrenia pathophysiology. Anatomical research on primates suggests that these regions may be subdivided into distinct, topographically organized functional territories according to their connectivity to the striatum. The aim of the present work was the reconstruction of dopaminergic midbrain subregions in healthy subjects and schizophrenic patients and the evaluation of their structural connectivity profiles. Materials and Methods: A hypothesis-driven connectivity-based parcellation derived from diffusion tractography was applied on 24 healthy subjects and 30 schizophrenic patients to identify distinct territories within the human dopaminergic midbrain in vivo and non-invasively. Results: We identified a tripartite subdivision of dopaminergic midbrain, including limbic, prefrontal and sensorimotor territories. No significant differences in structural features or connectivity were found between subjects and patients. Conclusions: The parcellation scheme proposed herein may help to achieve detailed characterization of structural and functional anomalies of the dopaminergic midbrain in schizophrenic patients.

Anatomical Characterization of the Human Structural Connectivity between the Pedunculopontine Nucleus and Globus Pallidus via Multi-Shell Multi-Tissue Tractography.

Background and objectives: The internal (GPi) and external segments (GPe) of the globus pallidus represent key nodes in the basal ganglia system. Connections to and from pallidal segments are topographically organized, delineating limbic, associative and sensorimotor territories. The topography of pallidal afferent and efferent connections with brainstem structures has been poorly investigated. In this study we sought to characterize in-vivo connections between the globus pallidus and the pedunculopontine nucleus (PPN) via diffusion tractography. Materials and Methods: We employed structural and diffusion data of 100 subjects from the Human Connectome Project repository in order to reconstruct the connections between the PPN and the globus pallidus, employing higher order tractography techniques. We assessed streamline count of the reconstructed bundles and investigated spatial relations between pallidal voxels connected to the PPN and pallidal limbic, associative and sensorimotor functional territories. Results: We successfully reconstructed pallidotegmental tracts for the GPi and GPe in all subjects. The number of streamlines connecting the PPN with the GPi was greater than the number of those joining it with the GPe. PPN maps within pallidal segments exhibited a distinctive spatial organization, being localized in the ventromedial portion of the GPi and in the ventral-anterior portion in the GPe. Regarding their spatial relations with tractography-derived maps of pallidal functional territories, the highest value of percentage overlap was noticed between PPN maps and the associative territory. Conclusions: We successfully reconstructed the anatomical course of the pallidotegmental pathways and comprehensively characterized their topographical arrangement within both pallidal segments. PPM maps were localized in the ventromedial aspect of the GPi, while they occupied the anterior pole and the most ventral portion of the GPe. A better understanding of the spatial and topographical arrangement of the pallidotegmental pathways may have pathophysiological and therapeutic implications in movement disorders.

Microscopic reconstruction and immunohistochemical analysis of discomalleolar ligament.

Discomalleolar ligament represents the vestiges of the primitive lateral pterygoid muscle which penetrates in the caudal end of Meckel's cartilage; during the development of newborn, the petrotympanic fissure close almost completely leaving inside the discomalleolar ligament. After entering in tympanic cavity, some fibers of the discomalleolar ligament insert to walls of cavity, other fibers continue with the lateral margin of the anterior ligament and insert in the neck of malleus; in contrast, other Authors demonstrated that discomalleolar ligament is an independent structure inserted in proximity of the neck of the malleus. Although the discomalleolar ligament can be considered as a structure of clinical importance, it is not described by anatomy textbooks. Moreover, it is likely that important correlations between temporomandibular diseases and otological symptoms exist. We have studied discomalleolar ligament submitting the specimens to the 3D volume rendering technique, light microscopy, reconstructing a wide light microscopic fields to analyze the real connection between retrodiscal connective tissue and middle ear, and immunofluorescence methods in order to analyze the consistence of ligament. We have shown two types of connections between TMJ and ear: first, with external acoustic meatus and, second, with middle ear through discomalleolar ligament. The different insertion represents a strong support in order to demonstrate that the TMJ disorders can determine variations of tension that are transmitted on the tympanic membrane provoking tinnitus in according to clinical features. Then, we propose that it is necessary to mention, also in anatomy textbook, the discomalleolar ligament as ligament distance of TMJ.

Spatially coherent and topographically organized pathways of the human globus pallidus.

Internal and external segments of globus pallidus (GP) exert different functions in basal ganglia circuitry, despite their main connectional systems share the same topographical organization, delineating limbic, associative, and sensorimotor territories. The identification of internal GP sensorimotor territory has therapeutic implications in functional neurosurgery settings. This study is aimed at assessing the spatial coherence of striatopallidal, subthalamopallidal, and pallidothalamic pathways by using tractography-derived connectivity-based parcellation (CBP) on high quality diffusion MRI data of 100 unrelated healthy subjects from the Human Connectome Project. A two-stage hypothesis-driven CBP approach has been carried out on the internal and external GP. Dice coefficient between functionally homologous pairs of pallidal maps has been computed. In addition, reproducibility of parcellation according to different pathways of interest has been investigated, as well as spatial relations between connectivity maps and existing optimal stimulation points for dystonic patients. The spatial organization of connectivity clusters revealed anterior limbic, intermediate associative and posterior sensorimotor maps within both internal and external GP. Dice coefficients showed high degree of coherence between functionally similar maps derived from the different bundles of interest. Sensorimotor maps derived from the subthalamopallidal pathway resulted to be the nearest to known optimal pallidal stimulation sites for dystonic patients. Our findings suggest that functionally homologous afferent and efferent connections may share similar spatial territory within the GP and that subcortical pallidal connectional systems may have distinct implications in the treatment of movement disorders.