Should the Globus Pallidus Targeting Be Refined in Dystonia?

Background and Study Aims Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a highly effective therapy for primary generalized and focal dystonias, but therapeutic success is compromised by a nonresponder rate of up to 20%. Variability in electrode placement and in tissue stimulated inside the GPi may explain in part different outcomes among patients. Refinement of the target within the pallidal area could be helpful for surgery planning and clinical outcomes. The objective of this study was to discuss current and potential methodological (somatotopy, neuroimaging, and neurophysiology) aspects that might assist neurosurgical targeting of the GPi, aiming to treat generalized or focal dystonia. Methods We selected published studies by searching electronic databases and scanning the reference lists for articles that examined the anatomical and electrophysiologic aspects of the GPi in patients with idiopathic/inherited dystonia who underwent functional neurosurgical procedures. Results The sensorimotor sector of the GPi was the best target to treat dystonic symptoms, and was localized at its lateral posteroventral portion. The effective volume of tissue activated (VTA) to treat dystonia had a mean volume of 153 mm3 in the posterior GPi area. Initial tractography studies evaluated the close relation between the electrode localization and pallidothalamic tract to control dystonic symptoms.Regarding the somatotopy, the more ventral, lateral, and posterior areas of the GPi are associated with orofacial and cervical representation. In contrast, the more dorsal, medial, and anterior areas are associated with the lower limbs; between those areas, there is the representation of the upper limb. Excessive pallidal synchronization has a peak at the theta band of 3 to 8 Hz, which might be responsible for generating dystonic symptoms. Conclusions Somatotopy assessment of posteroventral GPi contributes to target-specific GPi sectors related to segmental body symptoms. Tractography delineates GPi output pathways that might guide electrode implants, and electrophysiology might assist in pointing out areas of excessive theta synchronization. Finally, the identification of oscillatory electrophysiologic features that correlate with symptoms might enable closed-loop approaches in the future.

Validating Patient-Specific Finite Element Models of Direct Electrocortical Stimulation

Direct electrocortical stimulation (DECS) with electrocorticography electrodes is an established therapy for epilepsy and an emerging application for stroke rehabilitation and brain-computer interfaces. However, the electrophysiological mechanisms that result in a therapeutic effect remain unclear. Patient-specific computational models are promising tools to predict the voltages in the brain and better understand the neural and clinical response to DECS, but the accuracy of such models has not been directly validated in humans. A key hurdle to modeling DECS is accurately locating the electrodes on the cortical surface due to brain shift after electrode implantation. Despite the inherent uncertainty introduced by brain shift, the effects of electrode localization parameters have not been investigated. The goal of this study was to validate patient-specific computational models of DECS against in vivo voltage recordings obtained during DECS and quantify the effects of electrode localization parameters on simulated voltages on the cortical surface. We measured intracranial voltages in six epilepsy patients during DECS and investigated the following electrode localization parameters: principal axis, Hermes, and Dykstra electrode projection methods combined with 0, 1, and 2 mm of cerebral spinal fluid (CSF) below the electrodes. Greater CSF depth between the electrode and cortical surface increased model errors and decreased predicted voltage accuracy. The electrode localization parameters that best estimated the recorded voltages across six patients with varying amounts of brain shift were the Hermes projection method and a CSF depth of 0 mm (r = 0.92 and linear regression slope = 1.21). These results are the first to quantify the effects of electrode localization parameters with in vivo intracranial recordings and may serve as the basis for future studies investigating the neuronal and clinical effects of DECS for epilepsy, stroke, and other emerging closed-loop applications.

MRI and CT Fusion in Stereotactic Electroencephalography: A Literature Review

Epilepsy is a common neurological disease characterized by spontaneous recurrent seizures. Resection of the epileptogenic tissue may be needed in approximately 25% of all cases due to ineffective treatment with anti-epileptic drugs. The surgical intervention depends on the correct detection of epileptogenic zones. The detection relies on invasive diagnostic techniques such as Stereotactic Electroencephalography (SEEG), which uses multi-modal fusion to aid localizing electrodes, using pre-surgical magnetic resonance and intra-surgical computer tomography as the input images. Moreover, it is essential to know how to measure the performance of fusion methods in the presence of external objects, such as electrodes. In this paper, a literature review is presented, applying the methodology proposed by Kitchenham to determine the main techniques of multi-modal brain image fusion, the most relevant performance metrics, and the main fusion tools. The search was conducted using the databases and search engines of Scopus, IEEE, PubMed, Springer, and Google Scholar, resulting in 15 primary source articles. The literature review found that rigid registration was the most used technique when electrode localization in SEEG is required, which was the proposed method in nine of the found articles. However, there is a lack of standard validation metrics, which makes the performance measurement difficult when external objects are presented, caused primarily by the absence of a gold-standard dataset for comparison.

Accurate localization of linear probe electrodes across multiple brains

Recently developed silicon probes have large numbers of recording electrodes on long linear shanks. Specifically, Neuropixels probes have 960 recording electrodes distributed over 9.6 mm shanks. Because of their length, Neuropixels probe recordings in rodents naturally span multiple brain areas. Typical studies collate recordings across several recording sessions and animals. Neurons recorded in different sessions and animals have to be aligned to each other and to a standardized brain coordinate system. Here we report a workflow for accurate localization of individual electrodes in standardized coordinates and aligned across individual brains. This workflow relies on imaging brains with fluorescent probe tracks and warping 3-dimensional image stacks to standardized brain atlases. Electrophysiological features are then used to anchor particular electrodes along the reconstructed tracks to specific locations in the brain atlas and therefore to specific brain structures. We performed ground-truth experiments, in which motor cortex outputs are labelled with ChR2 and a fluorescence protein. Recording from brain regions targeted by these outputs reveals better than 100 μm accuracy for electrode localization.

Comparison of 3T and 7T MRI for the visualization of globus pallidus sub-segments

The success of deep brain stimulation (DBS) targeting the internal globus pallidus (GPi) depends on the accuracy of electrode localization inside the GPi. In this study, we sought to compare visualization of the medial medullary lamina (MML) and accessory medullary lamina (AML) between proton density-weighted (PDW) and T2-weighted (T2W) sequences on 3T and 7T MRI scanners. Eleven healthy participants (five men and six women; age, 19–28 years; mean, 21.5) and one 61-year-old man were scanned using two-dimensional turbo spin-echo PDW and T2W sequences on 3T and 7T MRI scanners with a 32-channel receiver head coil and a single-channel transmission coil. Profiles of signal intensity were obtained from the pixel values of straight lines over the GP regions crossing the MML and AML. Contrast ratios (CRs) for GPe/MML, GPie/MML, GPie/AML, and GPii/AML were calculated. Qualitatively, 7T visualized both the MML and AML, whereas 3T visualized the MML less clearly and hardly depicted the AML. The T2W sequence at 7T yielded significantly higher CRs for GPie/MML, GPie/AML, and GPii/AML than the PDW sequence at 7T or 3T. The T2W sequence at 7T allows visualization of the internal structures of GPi segments with high signal intensity and contrast.