Limbic-motor areas interactions as revealed by Constrained Spherical Deconvolution tractography: a mechanism to shape complex motor behaviors?

Although there are several evidences in animal research on the emotional motor-limbic subcortical system including amygdala, hyppocampus, parahyppocampal cortex and nucleus accumbens, little is known about its connections to cortical motor-related areas. All these structures are in a position to influence behavior via cortical motor-related areas, which in turn have access, both directly and indirectly, to descending motor pathways. If on the one hand, many animal studies have investigated the neural connectivity of the motor-limbic system using electrophysiological and tracing techniques, on the other hand the use of these methods in the live human brain is limited and elusive due to their invasive nature [1]. By contrast, recent developments in diffusion magnetic resonance imaging and tractography have allowed for non-invasive and in vivo investigation of the human brain. Diffusion-based tractography is a method analyzing the preferential water diffusivity directionality along white matter bundles, thus calculating the highest mathematical probability that water diffuses in a given direction [2]. Using diffusion-weighted magnetic resonance imaging and Constrained Spherical Deconvolution tractography on a population of 15 healthy subjects, we provided tractographic evidence of a structural connection between the amygdala and motor-related areas in humans. These direct limbic-motor pathways may allow for the regulation and modulation of complex motor behaviors and subtle behaviors such as social interactions. The demonstration of these interactions might be fundamental for the comprehension of the pathophysiology of several limbic-sensorimotor diseases, such autism spectrum disorders and motor conversion disorders

Endogenous orientation of visual attention in auditory space

Visuospatial attention is asymmetrically distributed with a leftward bias (i.e. pseudoneglect), while evidence for asymmetries in auditory spatial attention is still controversial. In the present study, we investigated putative asymmetries in the distribution of auditory spatial attention and the influence that visual information might have on its deployment. A modified version of the Posner task (i.e. the visuo-audio spatial task [VAST]) was used to investigate spatial processing of auditory targets when endogenous orientation of spatial attention was mediated by visual cues in healthy adults. A line bisection task (LBT) was also administered to assess the presence of a leftward bias in deployment of visuospatial attention. Overall, participants showed rightward and leftward biases in the VAST and the LBT, respectively. In the VAST, sound localization was enhanced by visual cues. Altogether, these findings support the existence of a facilitation effect for auditory targets originating from the right side of space and provide new evidence for crossmodal links in endogenous spatial attention between vision and audition

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

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Network analysis shows decreased ipsilesional structural connectivity in glioma patients

Tumors and their location distinctly alter both local and global brain connectivity within the ipsilesional hemisphere of glioma patients. Gliomas that infiltrate networks and systems, such as the motor system, often lead to substantial functional impairment in multiple systems. Network-based statistics (NBS) allow to assess local network differences and graph theoretical analyses enable investigation of global and local network properties. Here, we used network measures to characterize glioma-related decreases in structural connectivity by comparing the ipsi- with the contralesional hemispheres of patients and correlated findings with neurological assessment. We found that lesion location resulted in differential impairment of both short and long connectivity patterns. Network analysis showed reduced global and local efficiency in the ipsilesional hemisphere compared to the contralesional hemispheric networks, which reflect the impairment of information transfer across different regions of a network.Peer reviewe

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

Moving into the wide clinical spectrum of consciousness disorders: Pearls, perils and pitfalls

The last few years have been characterized by a growing interest of the medical and scientific world for the field of consciousness and its related disorders. Medically speaking, conscious- ness can be defined as the state of awareness of self and environment and the alertness to external stimulation, besides responsiveness to inner need. Transient loss of consciousness can be due to alterations in cerebral blood flow leading to fainting or syncope, migraine, metabolic dysfunctions, unexpected intracranial pressure increases, epileptic seizures, and sleep disorders. Chronic disorders of consciousness are a tragic success of high-technology treatment, in an attempt to maintain or reestablish brain function, which is to be considered as the main goal of therapeutics. Management of vegetative or a minimally conscious state individuals involves charily getting the right diagnosis with an evidence-based prognosis, also taking into account the medical, ethical, and legal key factors of the ideal treatment. This paper is aimed at exploring the wide spectrum of consciousness disorders and their clinical differential diagnosis, with particular regards to those with a negative impact on patient and their caregiver quality of life, including epilepsy, sleep disorders, and vegetative/minimally conscious state

Constrained spherical deconvolution provides evidence of extensive subcortical direct cerebellumbasal ganglia connections in human brain

Traditionally, the basal ganglia (BG) are thought to play a major role in the selection and inhibition of motor commands, while the cerebellum plays a role in tuning and reshaping on-going movement. In the past, the connections between the cerebellum and the cerebral cortex have been considered to be anatomically and functionally distinct from those linking the BG with the cerebral cortex. Evidences from recent anatomical experiments, using retrograde transneuronal transport of rabies virus in macaques, have challenged this old perspective demonstrating disynaptic subcortical pathways that directly link the cerebellum with the BG. Since the application of these techniques to the human brain remains elusive, due to the invasive nature of such methods, whether and to what extent these specific connections between the BG and cerebellum exist in the human brain remains unclear. However, recent developments in Diffusion Magnetic Resonance Imaging (dMRI) and diffusion tractography may allow for non-invasive and in vivo studies of the anatomical substrate of basal ganglia systems. Indeed, in our previous paper we studied the basal ganglia connectome providing strong evidences of a direct connection from cortex to Globus Pallidum (GPe and GPi) [1]. Thirteen normal subjects with no history of any overt neurological and/or psychiatric disorders were examined to test the hypotheses that substantial interactions, at least on the level shown in animal studies, also exist in the human brain. We demonstrated that it is feasible to disclose these cerebellar-subcortical connections by using constrained spherical deconvolution (CSD), an innovative approach which allows a reliable reconstruction of small- and long-fiber pathways, with subvoxel resolution in brain regions with multiple fiber orientations [2]. In particular we found evidences of subthalamic-cerebellar, dentate-thalamo-striatal, dentate-rubral-thalamic, dentate-rubral-pallidal and dentate-nigral connections. In addition to these connections, we found a direct cerebellar-dentate-pallidal connection never reported in literature to our knowledge; we identified and isolated two well-distinct tracts presenting an ipsilateral and contralateral component, converging mainly on the antero-medial part of the globus pallidus

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