Introduction: Models of structural connectivity in the human brain are typically simulated using tractographic approaches. However, the nonlinear fitting of anatomical pathway atlases to de novo subject brains represents a simpler alternative that is hypothesized to provide more anatomically realistic results. Therefore, the goal of this study was to perform a side-by-side comparison of the streamline estimates generated by either pathway atlas fits or tractographic reconstructions in the same subjects. Methods: Our analyses focused on reconstruction of the corticospinal tract (CST), cerebellothalamic (CBT), and pallidothalamic (PT) pathways using example datasets from the Human Connectome Project (HCP). We used MRtrix3 to explore whole brain, as well as manual seed-to-target, tractography approaches. In parallel, we performed nonlinear fits of an axonal pathway atlas to each HCP dataset using Advanced Normalization Tools (ANTs). Results: The different methods produced notably different estimates for each pathway in each subject. The fitted atlas pathways were highly stereotyped and exhibited low variability in their streamline trajectories. Manual tractography resulted in pathway estimates that generally corresponded with the fitted atlas pathways, but with a higher degree of variability in the individual streamlines. Pathway reconstructions derived from whole-brain tractography exhibited the highest degree of variability and struggled to create anatomically realistic representations for either the CBT or PT pathways. Conclusion: The speed, simplicity, reproducibility, and realism of anatomical pathway model fits makes them an appealing option for some forms of structural connectivity modeling in the human brain. Impact statement Axonal pathway modeling is an important component of deep brain stimulation (DBS) research studies that seek to identify the brain connections that are directly activated by stimulation. The corticospinal tract, cerebellothalamic (CBT), and pallidothalamic (PT) pathways are specifically relevant to the study of subthalamic DBS for the treatment of Parkinson's disease. Our results suggest that anatomical pathway model fits of the CBT and PT pathways to de novo subject brains represent a more anatomically realistic option than tractographic approaches when studying subthalamic DBS.

The output network of the basal ganglia plays an important role in motor, associative, and limbic processing and is generally characterized by the pallidothalamic and nigrothalamic pathways. However, these connections in the human brain remain difficult to elucidate because of the resolution limit of current neuroimaging techniques. The present study aimed to investigate the mesoscopic nature of these connections between the thalamus, substantia nigra pars reticulata, and globus pallidus internal segment using 7 Tesla (7T) magnetic resonance imaging (MRI). In this study, track-density imaging (TDI) of the whole human brain was employed to overcome the limitations of observing the pallidothalamic and nigrothalamic tracts. Owing to the super-resolution of the TD images, the substructures of the SN, as well as the associated tracts, were identified. This study demonstrates that 7T MRI and MR tractography can be used to visualize anatomical details, as well as 3D reconstruction, of the output projections of the basal ganglia.

The aim of this study was to make a thorough investigation of the trajectory of the ansa lenticularis (AL) and its subcomponents using high-resolution fiber-tracking tractography. The subcomponents of the AL were reconstructed from one region of interest (ROI) in the area of the globus pallidus combined with another ROI in the red nucleus, substantia nigra, subthalamic nucleus, or thalamus. This fiber-tracking protocol was tested in an HCP-1065 template, 35 healthy subjects from Massachusetts General Hospital (MGH), and 20 healthy subjects from the human connectome project (HCP) using generalized q-sampling imaging (GQI)-based tractography. Quantitative anisotropy and fractional anisotropy were also computed for the AL subcomponents. The subcomponents of the AL could be reconstructed in the HCP-1065 template, 35 MGH healthy subjects, and 20 HCP healthy subjects. The AL descends from the globus pallidus and joins the ansa peduncularis for a short distance, subdividing later into fibers that continue separately to the red nucleus, substantia nigra, subthalamic nucleus, and thalamus. The study demonstrated the trajectory of the ansa lenticularis and its subcomponents using GQI-based tractography, improving our understanding of the anatomical connectivity between the globus pallidus and the thalamo-subthalamic region in the human brain. One Sentence Summary The investigation of the ansa lenticularis and its subcomponents using high-resolution diffusion images based tractography.

The human hypothalamus is composed of several gray matter territories, forming 10 different structures mainly referred to as nuclei: the preoptic, suprachiasmatic, supraoptic, infundibular, paraventricular, dorsomedial, ventromedial, posterior (dorsal; dorsal hypothalamic area), and tuberomamillary nuclei, and the lateral hypothalamic area. The macroconnectivity, described since the middle of the 19th century, is currently probed using MRI methods, notably those relying on diffusion techniques. The structural connections can be grouped as follows: connections with the olfactory system; stria terminalis connections; stria medullaris connections; ansa lenticularis connections; subthalamus connections; optic tract connections; intrahypothalamic connections; hypothalamo-hypophysis connections; hypothalamic commissures; cortex connections.

The anatomy of the pallidothalamic tracts, including the ansa lenticularis, lenticular fasciculus, and thalamic fasciculus (field H1 of Forel), should be elucidated by neurosurgeons and neuroscientists who study deep brain stimulation. In this study, serially sectioned images of a human cadaver head were employed to overcome the limitations of existing methods to observe the pallidothalamic tracts. Owing to the high resolution and real color of the sectioned images, 28 structures, including the pallidothalamic tracts and mammillothalamic fasciculus, were identified. The structures were segmented and made into surface models, which are helpful in improving the stereoscopic understanding. Observing the sectioned images and surface models may help in understanding the detailed anatomy of the pallidothalamic tracts. The new findings, such as the spatial relationship of the tracts, were summarized in a schematic figure. Moreover, to elucidate the anatomical structures along the course of deep brain stimulation, virtual electrodes were inserted into the surface models. The sectioned images and surface models of this study are expected to enhance the understanding of the pallidothalamic tract anatomy. A portable document format file containing the surface models and the sectioned images can be freely downloaded from the authors' homepage. Clin. Anat. 32:66-76, 2019. © 2019 Wiley Periodicals, Inc.

In a previous report showing white matter microstructural hemispheric asymmetries medial to the pallidum in focal dystonias, we showed preliminary evidence that this abnormality was reduced 4 weeks after botulinum toxin (BTX) injections. In the current study we report the completed treatment study in a full-size cohort of CD patients (n = 14). In addition to showing a shift toward normalization of the hemispheric asymmetry, we evaluated clinical relevance of these findings by relating white matter changes to degree of symptom improvement. We also evaluated whether the magnitude of the white matter asymmetry before treatment was related to severity, laterality, duration of dystonia, and/or number of previous BTX injections. Our results confirm the findings of our preliminary report: we observed significant fractional anisotropy (FA) changes medial to the pallidum 4 weeks after BTX in CD participants that were not observed in controls scanned at the same interval. There was a significant relationship between magnitude of hemispheric asymmetry and dystonia symptom improvement, as measured by percent reduction in dystonia scale scores. There was also a trend toward a relationship between magnitude of pre-injection white matter asymmetry and symptom severity, but not symptom laterality, disorder duration, or number of previous BTX injections. Post-hoc analyses suggested the FA changes at least partially reflected changes in pathophysiology, but a dissociation between patient perception of benefit from injections and FA changes suggested the changes did not reflect changes to the primary "driver" of the dystonia. In contrast, there were no changes or group differences in DTI diffusivity measures, suggesting the hemispheric asymmetry in CD does not reflect irreversible white matter tissue loss. These findings support the hypothesis that central nervous system white matter changes are involved in the mechanism by which BTX exerts clinical benefit.