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The subthalamic nucleus, substantia nigra, and globus pallidus, three nuclei of the human basal ganglia, play an important role in motor, associative, and limbic processing. The network of the basal ganglia is generally characterized by a direct, indirect, and hyperdirect pathway. This study aims to investigate the mesoscopic nature of these connections between the subthalamic nucleus, substantia nigra, and globus pallidus and their surrounding structures. A human post mortem brain specimen including the substantia nigra, subthalamic nucleus, and globus pallidus was scanned on a 7 T MRI scanner. High resolution diffusion weighted images were used to reconstruct the fibers intersecting the substantia nigra, subthalamic nucleus, and globus pallidus. The course and density of these tracks was analyzed. Most of the commonly established projections of the subthalamic nucleus, substantia nigra, and globus pallidus were successfully reconstructed. However, some of the reconstructed fiber tracks such as the connections of the substantia nigra pars compacta to the other included nuclei and the connections with the anterior commissure have not been shown previously. In addition, the quantitative tractography approach showed a typical degree of connectivity previously not documented. An example is the relatively larger projections of the subthalamic nucleus to the substantia nigra pars reticulata when compared to the projections to the globus pallidus internus. This study shows that ultra-high field post mortem tractography allows for detailed 3D reconstruction of the projections of deep brain structures in humans. Although the results should be interpreted carefully, the newly identified connections contribute to our understanding of the basal ganglia.

Deep brain stimulation of the subthalamic nucleus (STN) is a widely performed surgical treatment for patients with Parkinson's disease. The goal of the surgery is to place an electrode centered in the motor region of the STN while lowering the effects of electrical stimulation on the non-motor regions. However, distinguishing the motor region from the neighboring associative and limbic areas in individual patients using imaging modalities was until recently difficult to obtain in vivo. Here, using ultra-high field MR imaging, we have performed a dissection of the subdivisions of the STN of individual Parkinson's disease patients. We have acquired 7T diffusion-weighted images of seventeen patients with Parkinson's disease scheduled for deep brain stimulation surgery. Using a structural connectivity-based parcellation protocol, the STN's connections to the motor, limbic, and associative cortical areas were used to map the individual subdivisions of the nucleus. A reproducible patient-specific parcellation of the STN into a posterolateral motor and gradually overlapping central associative area was found in all STNs, taking up on average 55.3% and 55.6% of the total nucleus volume. The limbic area was found in the anteromedial part of the nucleus. Our results suggest that 7T MR imaging may facilitate individualized and highly specific planning of deep brain stimulation surgery of the STN. •The subthalamic nucleus of individual Parkinson patients was parcellated at 7T MRI.•A motor zone was found posterolaterally.•Associative and limbic zones were found more anteriorly and anteromedially.•A gradual overlap of the functional zones was found within the STN.

Abstract BACKGROUND Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) can improve seizure control for patients with drug-resistant epilepsy (DRE). Yet, one cannot overlook the high discrepancy in efficacy among patients, possibly resulting from differences in stimulation site. OBJECTIVE To test the hypothesis that stimulation at the junction of the ANT and mammillothalamic tract (ANT-MTT junction) increases seizure control. METHODS The relationship between seizure control and the location of the active contacts to the ANT-MTT junction was investigated in 20 patients treated with ANT-DBS for DRE. Coordinates and Euclidean distance of the active contacts relative to the ANT-MTT junction were calculated and related to seizure control. Stimulation sites were mapped by modelling the volume of tissue activation (VTA) and generating stimulation heat maps. RESULTS After 1 yr of stimulation, patients had a median 46% reduction in total seizure frequency, 50% were responders, and 20% of patients were seizure-free. The Euclidean distance of the active contacts to the ANT-MTT junction correlates to change in seizure frequency (r2 = 0.24, P = .01) and is ∼30% smaller (P = .015) in responders than in non-responders. VTA models and stimulation heat maps indicate a hot-spot at the ANT-MTT junction for responders, whereas non-responders had no evident hot-spot. CONCLUSION Stimulation at the ANT-MTT junction correlates to increased seizure control. Our findings suggest a relationship between the stimulation site and therapy response in ANT-DBS for epilepsy with a potential role for the MTT. DBS directed at white matter merits further exploration for the treatment of epilepsy. Graphical Abstract Graphical Abstract

Graphical Abstract Graphical Abstract

Deep brain stimulation is a treatment for Parkinson's disease and other related disorders, involving the surgical placement of electrodes in the deeply situated basal ganglia or thalamic structures. Good clinical outcome requires accurate targeting. However, due to limited visibility of the target structures on routine clinical MR images, direct targeting of structures can be challenging. Non-clinical MR scanners with ultra-high magnetic field (7T or higher) have the potential to improve the quality of these images. This technology report provides an overview of the current possibilities of visualizing deep brain stimulation targets and their related structures with the aid of ultra-high field MRI. Reviewed studies showed improved resolution, contrast- and signal-to-noise ratios at ultra-high field. Sequences sensitive to magnetic susceptibility such as T2(*) and susceptibility weighted imaging and their maps in general showed the best visualization of target structures, including a separation between the subthalamic nucleus and the substantia nigra, the lamina pallidi medialis and lamina pallidi incompleta within the globus pallidus and substructures of the thalamus, including the ventral intermediate nucleus (Vim). This shows that the visibility, identification, and even subdivision of the small deep brain stimulation targets benefit from increased field strength. Although ultra-high field MR imaging is associated with increased risk of geometrical distortions, it has been shown that these distortions can be avoided or corrected to the extent where the effects are limited. The availability of ultra-high field MR scanners for humans seems to provide opportunities for a more accurate targeting for deep brain stimulation in patients with Parkinson's disease and related disorders.