Structural connectivity‐based topography of the human globus pallidus: Implications for therapeutic targeting in movement disorders

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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

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

The cerebellum-periaqueductal gray connectivity: a constrained spherical deconvolution tractography study

The periaqueductal gray (PAG) is a relevant neuronal station situated in the midbrain, which play a pivotal role in triggering behavioral responses to stressful stimuli, such as pain or threat. Current knowledge concerning PAG functions is based on several tract-tracing studies conducted on animals, which unveiled PAG connectivity to both cortical and subcortical areas [1]. Considering that descending projections to spinal cord reach the dorsal horn and connections to motor related cortical areas have never been described yet, the neural structure which best fits PAG modulation of motor behavior is the cerebellum. Direct connections between PAG and cerebellar cortex were firstly described in cats and neurophysiological studies conducted on animals, suggesting either direct or undirect PAG influence to cerebellar activity. In the last decades, the rise of diffusion weighted imaging and tractography have made possible to reliably reconstruct white matter pathways in the human brain. To the best of our knowledge, few tractography studies explored PAG connectivity in humans and the evidences concerning direct or undirect connections with the cerebellar cortex are still sparse. Aimed at investigating PAG connectivity with particular focus on PAG-cerebellum connections, we used high quality diffusion weighted imaging data of thirty healthy subjects from the Human Connectome Project. Fiber tracts have been reconstructed using Spherical Informed Filtering of Tractograms, a novel algorithm improving streamline reconstruction and selection [2]. Connectivity analysis revealed that the PAG is mainly connected with subcortical structures, such as the thalamus and the cerebellum. Taken together our results show a direct interplay between the PAG and the cerebellum, thus suggesting the cerebellum as a likely candidate to modulate complex features of motor behavior in stressful conditions, such as adaptation after social defeat and computing strategies to avoid threatening situations

In-vivo anatomical reconstruction of the optic radiations in the human brain

The optic radiations are major white matter pathways funneling visual information from the lateral geniculate nuclei to the visual cortex in the occipital lobe. Given their relevance in visual processing and in several brain disorders, the optic radiations have been extensively investigated by using magnetic resonance imaging and diffusion tensor imaging tractography [1]. Herein, we use a powerful diffusion signal modeling, namely Constrained Spherical Deconvolution, in order to provide an exhaustive connectivity profile of the connections between the lateral geniculate nucleus and the visual cortex in the healthy brain, as well as pulvinar connectivity with visual-related structures. In addition, taking into account that visual deficits may precede motor symptoms’ onset in Parkinson’s Disease [2], we assessed whether the intracranial visual system can be involved at the early stage of the disease. Our connectivity analysis revealed that the optic radiations are mainly distributed in V1 and V2. Furthermore, we found significant alterations of optic radiations connectivity distribution in Parkinson’s Disease patients, with decreased lateral geniculate nucleus-V2 density as well as significant increase of optic radiations’ mean diffusivity. Voxel Based Morphometry analysis also showed significant reduction of visual cortical volumes and of the optic radiation in the patients group. In conclusion, our findings provide a reliable connectivity profile of the optic radiations, suggesting extrastriate-lateral geniculate nucleus connections in human brain. Finally, we showed that visual system alterations can be detected at early stages of Parkinson’s Disease

Clinical correlates of "pure" essential tremor: the TITAN study

BackgroundTo date, there are no large studies delineating the clinical correlates of "pure" essential tremor (ET) according to its new definition.MethodsFrom the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of "pure" ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum.ResultsOut of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) "pure" ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options.DiscussionThe findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of "pure" ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of "pure" ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies

Copernicus Ocean State Report, issue 6

The 6th issue of the Copernicus OSR incorporates a large range of topics for the blue, white and green ocean for all European regional seas, and the global ocean over 1993–2020 with a special focus on 2020

Clinical correlates of “pure” essential tremor: the TITAN study

BackgroundTo date, there are no large studies delineating the clinical correlates of “pure” essential tremor (ET) according to its new definition.MethodsFrom the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of “pure” ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum.ResultsOut of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) “pure” ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options.DiscussionThe findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of “pure” ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of “pure” ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies