Lateral hypothalamic area deep brain stimulation for refractory obesity: a pilot study with preliminary data on safety, body weight, and energy metabolism.

OBJECT: Deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) has been suggested as a potential treatment for intractable obesity. The authors present the 2-year safety results as well as early efficacy and metabolic effects in 3 patients undergoing bilateral LHA DBS in the first study of this approach in humans. METHODS: Three patients meeting strict criteria for intractable obesity, including failed bariatric surgery, underwent bilateral implantation of LHA DBS electrodes as part of an institutional review board- and FDA-approved pilot study. The primary focus of the study was safety; however, the authors also received approval to collect data on early efficacy including weight change and energy metabolism. RESULTS: No serious adverse effects, including detrimental psychological consequences, were observed with continuous LHA DBS after a mean follow-up of 35 months (range 30-39 months). Three-dimensional nonlinear transformation of postoperative imaging superimposed onto brain atlas anatomy was used to confirm and study DBS contact proximity to the LHA. No significant weight loss trends were seen when DBS was programmed using standard settings derived from movement disorder DBS surgery. However, promising weight loss trends have been observed when monopolar DBS stimulation has been applied via specific contacts found to increase the resting metabolic rate measured in a respiratory chamber. CONCLUSIONS: Deep brain stimulation of the LHA may be applied safely to humans with intractable obesity. Early evidence for some weight loss under metabolically optimized settings provides the first "proof of principle" for this novel antiobesity strategy. A larger follow-up study focused on efficacy along with a more rigorous metabolic analysis is planned to further explore the benefits and therapeutic mechanism behind this investigational therapy.

Three-dimensional somatotopic organization and probabilistic mapping of motor responses from the human internal capsule.

OBJECT: The somatotopic organization of the motor fibers within the posterior limb of the internal capsule (IC) in humans remains unclear. Several electrophysiological atlases created from stimulation during stereotactic neurosurgery have suggested that there is considerable overlap between representations of body parts. Overlap reported in these studies may have been due to linear scaling methods applied to the data that were unable to account for individual anatomical variability. In the current work, the authors attempted to overcome these limitations by using a nonlinear registration technique to better understand the spatial location and extent of the body-part representations in the IC. METHODS: Data were acquired during 30 cases of deep brain neurosurgery in which the IC was electrically stimulated to localize the ventrolateral nucleus for a subsequent thalamotomy or implantation of a thalamic deep brain stimulator. Motor responses from the tongue, face, arm, or leg were evoked in the IC and coded in the patient's native MR imaging space. The tagged MR images were then nonlinearly registered to a high-resolution template MR image. This work resulted in a functional electrophysiological atlas demonstrating the locations of body-part representations in the posterior limb of the IC that takes individual anatomical variability into account. To further understand the spatial location and extent of the motor responses, the electrophysiological data points were transformed into 3D probability maps that describe the likelihood of obtaining motor responses in the posterior limb of the IC. RESULTS: The analyses suggest a reliable face-anterior, arm-intermediate, and leg-posterior somatotopic organization in the posterior limb of the IC with little overlap between the body-part representations. CONCLUSIONS: This probabilistic atlas of functional responses evoked by stimulating the posterior limb of the IC provides better understanding of the anatomical organization of descending motor fibers, can be used for indirect intraoperative confirmation of the location of the ventrolateral thalamus, and is applicable to clinical and research MR imaging studies requiring information on spatial organization of motor fibers at the thalamic level in the human brain.

Visualization and navigation system development and application for stereotactic deep-brain neurosurgeries.

We present the development of a visualization and navigation system and its application in pre-operative planning and intra-operative guidance of stereotactic deep-brain neurosurgical procedures for the treatment of Parkinson's disease, chronic pain, and essential tremor. This system incorporates a variety of standardized functional and anatomical information, and is capable of non-rigid registration, interactive manipulation, and processing of clinical image data. The integration of a digitized and segmented brain atlas, an electrophysiological database, and collections of final surgical targets from previous patients facilitates the delineation of surgical targets and surrounding structures, as well as functional borders. We conducted studies to compare the surgical target locations identified by an experienced stereotactic neurosurgeon using multiple electrophysiological exploratory trajectories with those located by a non-expert using this system on 70 thalamotomy, pallidotomy, thalamic deep-brain stimulation (DBS), and subthalamic nucleus (STN) DBS procedures. The average displacement between the surgical target locations in both groups was 1.95 +/- 0.86 mm, 1.83 +/- 1.07 mm, 1.88 +/- 0.89 mm and 1.61 +/- 0.67 mm for each category of surgeries, respectively, indicating the potential value of our system in stereotactic deep-brain neurosurgical procedures, and demonstrating its capability for accurate surgical target initiation.

Comparison of different targeting methods for subthalamic nucleus deep brain stimulation.

The subthalamic nucleus (STN) has been adopted as a commonly used surgical target in deep brain stimulation (DBS) procedures for the treatment of Parkinson's disease. Many techniques have been developed to facilitate STN DBS targeting, and consequently to improve the surgical outcome. In this work, we conducted a retrospective study on 10 patients who were treated with bilateral STN DBS to assess the target localization accuracy and precision of six methods in STN DBS surgery. A visualization and navigation system integrated with normalized functional and anatomical information was employed to perform the targeting procedures. Actual surgical target location determined by an experienced neurosurgeon with pre-operative image-guided surgical target/trajectory planning and intra-operative electrophysiological exploration and confirmation was considered as the "gold standard" in this evaluation and was compared with those localized using each of the six targeting methods. The mean distance between the actual surgical targets and those planned was 3.0 +/- 1.3 mm, 3.2 +/- 1.1 mm, 2.9 +/- 1.1 mm, 2.7 +/- 1.2 mm, 2.5 +/- 1.0 mm, and 1.7 +/- 0.8 mm for targeting approaches based on T2-weighted magnetic resonance image (MRI), brain atlas, T1 and T2 maps, electrophysiological database, collection of final surgical targets of previous patients, and the combination of these functional and anatomical data respectively. The results demonstrated that the use of functional data along with anatomical data provides reliable and accurate target position for STN DBS.

Development and application of functional databases for planning deep-brain neurosurgical procedures.

This work presents the development and application of a visualization and navigation system for planning deep-brain neurosurgeries. This system, which incorporates a digitized and segmented brain atlas, an electrophysiological database, and collections of final surgical targets of previous patients, provides assistance for non-rigid registration, navigation, and reconstruction of clinical image data. The fusion of standardized anatomical and functional data, once registered to individual patient images, facilitates the delineation of surgical targets. Our preliminary studies compared the target locations identified by a non-expert using this system with those located by an experienced neurosurgeon using regular technique on 8 patients who had undergone subthalamic nucleus (STN) deep-brain stimulations (DBS). The average displacement between the surgical target locations in both groups was 0.58 mm +/- 0.49 mm, 0.70 mm +/- 0.37 mm, and 0.69 mm +/- 0.34 mm in x, y, and z directions respectively, indicating the capability of accurate surgical target initiation of our system, which has also shown promise in planning and guidance for other stereotactic deep-brain neurosurgical procedures.

Three-dimensional database of subcortical electrophysiology for image-guided stereotactic functional neurosurgery.

We present a method of constructing a database of intraoperatively observed human subcortical electrophysiology. In this approach, patient electrophysiological data are standardized using a multiparameter coding system, annotated to their respective magnetic resonance images (MRIs), and nonlinearly registered to a high-resolution MRI reference brain. Once registered, we are able to demonstrate clustering of like interpatient physiologic responses within the thalamus, globus pallidus, subthalamic nucleus, and adjacent structures. These data may in turn be registered to a three-dimensional patient MRI within our image-guided visualization program enabling prior to surgery the delineation of surgical targets, anatomy with high probability of containing specific cell types, and functional borders. The functional data were obtained from 88 patients (106 procedures) via microelectrode recording and electrical stimulation performed during stereotactic neurosurgery at the London Health Sciences Centre. Advantages of this method include the use of nonlinear registration to accommodate for interpatient anatomical variability and the avoidance of digitized versions of printed atlases of anatomy as a common database coordinate system. The resulting database is expandable, easily searched using a graphical user interface, and provides a visual representation of functional organization within the deep brain.