Charles Y. Liu

Decoding Motor Imagery from the Posterior Parietal Cortex of a Tetraplegic Human

Brain imagination to control external devices Studies in monkeys have implicated the brains posterior parietal cortex in high-level coding of planned and imagined actions. Aflalo et al. implanted two microelectrode arrays in the posterior parietal cortex of a tetraplegic patient (see the Perspective by Pruszynski and Diedrichsen). They asked the patient to imagine various types of limb or eye movements. As predicted, motor imagery involved the same types of neural population activity involved in actual movements, which could potentially be exploited in prosthetic limb control. Science, this issue p. 906; see also p. 860 Neurons in the human posterior parietal cortex encode high-level aspects of imagined movements. [Also see Perspective by Pruszynski and Diedrichsen] Nonhuman primate and human studies have suggested that populations of neurons in the posterior parietal cortex (PPC) may represent high-level aspects of action planning that can be used to control external devices as part of a brain-machine interface. However, there is no direct neuron-recording evidence that human PPC is involved in action planning, and the suitability of these signals for neuroprosthetic control has not been tested. We recorded neural population activity with arrays of microelectrodes implanted in the PPC of a tetraplegic subject. Motor imagery could be decoded from these neural populations, including imagined goals, trajectories, and types of movement. These findings indicate that the PPC of humans represents high-level, cognitive aspects of action and that the PPC can be a rich source for cognitive control signals for neural prosthetics that assist paralyzed patients.

Toward the Emergence of Nanoneurosurgery: Part III—Nanomedicine: Targeted Nanotherapy, Nanosurgery, and Progress Toward the Realization of Nanoneurosurgery

THE NOTION OF nanotechnology has evolved since its inception as a fantastic conceptual idea to its current position as a mainstream research initiative with broad applications among all divisions of science. In the first part of this series, we reviewed the structures and principles that comprise the main body of knowledge of nanoscience and nanotechnology. In the second part, we discussed applications of nanotechnology to the emerging field of nanomedicine, with specific attention on medical diagnostics and imaging. This article further explores the applications of nanotechnology to nanomedicine. Specific attention is given to developments in therapeutic modalities, including advanced drug delivery systems and targeted nanotherapy, which will form the basis for the treatment arm of mature nanomedicine. A variety of modalities are discussed, including polymeric nanoparticles, micelles, liposomes, dendrimers, fullerenes, hydrogels, nanoshells, and smart surfaces. Applications of nanotechnology to nanosurgery and nanoneurosurgery are presented. Femtosecond laser systems, nanoneedles, and nanotweezers are presented as technologies that are operational at the nanoscale level and have the potential to revolutionize the practice of neurosurgery in a profound and momentous way.

Vagus nerve stimulation therapy after failed cranial surgery for intractable epilepsy: results from the vagus nerve stimulation therapy patient outcome registry.

OBJECTIVE To determine the effectiveness of vagus nerve stimulation (VNS) therapy among patients with persistent or recurrent seizures after lobar resection, callosotomy, and other cranial operations for intractable epilepsy. METHODS Data were obtained from the VNS therapy patient outcome registry, which was established after United States Food and Drug Administration approval of the VNS device in 1997 as a means of capturing open-label clinical data outside of protocol. The integrity of the systems for collecting and processing registry data was authenticated by an independent auditing agency. The effect of potential selection bias, however, remains uncertain. RESULTS Two nonconsecutive cohorts were compared: patients tracked in the registry who had previously undergone cranial surgery for epilepsy (CS group, n=921) and those who had not (non-CS group, n = 3822). For the CS group, the median reduction in seizure frequency was 42.5% after 3 months of VNS therapy, 42.9% at 6 months, 45.7% at 12 months, 52.0% at 18 months, and 50.5% at 24 months. For the non-CS group, analogous rates were 47.0%, 52.9%, 60.0%, 62.7%, and 66.7%, respectively. In the CS group, seizures were reduced by at least 50% in 55.1% of patients, at least 75% in 31.4% of patients, at least 90% in 17.3% of patients, and 100% in 5.1% of patients after 24 months of VNS therapy. Response rates were more pronounced in the non-CS group: at least 50% in 62.2% of patients, at least 75% in 43.7% of patients, at least 90% in 26.8% of patients, and 100% in 8.3% of patients. Patients in both groups experienced marked improvements in quality of life parameters. CONCLUSION The effectiveness of VNS is maintained during prolonged stimulation, and overall seizure control continues to improve with time. Patients in whom prior cranial surgery had failed did not respond as favorably as all other patients receiving VNS therapy. Nonetheless, many of the former group improved substantially. Thus, on the basis of these open-label data, VNS therapy represents a potentially palliative treatment option for patients with refractory seizures after failed cranial surgery.

The genesis of neurosurgery and the evolution of the neurosurgical operative environment: part I-prehistory to 2003.

DESPITE ITS SINGULAR importance, little attention has been given to the neurosurgical operative environment in the scientific and medical literature. This article focuses attention on the development of neurosurgery and the parallel emergence of its operative setting. The operative environment has, to a large extent, defined the “state of the art and science” of neurosurgery, which is now undergoing rapid reinvention. During the course of its initial invention, major milestones in the development of neurosurgery have included the definition of anatomy, consolidation of a scientific basis, and incorporation of the practicalities of anesthesia and antisepsis and later operative technical adjuvants for further refinement of action and minimalism. The progress, previously long and laborious in emergence, is currently undergoing rapid evolution. Throughout its evolution, the discipline has assimilated the most effective tools of modernity into the operative environment, leading eventually to the entity known as the operating room.In the decades leading to the present, progressive minimalization of manipulation and the emergence of more refined operative definition with increasing precision are evident, with concurrent miniaturization of attendant computerized support systems, sensors, robotic interfaces, and imaging devices. These developments over time have led to the invention of neurosurgery and the establishment of the current state-of-the-art neurosurgical operating room as we understand it, and indeed, to a broader definition of the entity itself. To remain current, each neurosurgeon should periodically reconsider his or her personal operative environment and its functional design with reference to modernity of practice as currently defined.

Toward the emergence of nanoneurosurgery: Part II-Nanomedicine : Diagnostics and imaging at the nanoscale level

THE NOTION OF nanotechnology has evolved since its inception as a fantastic conceptual idea to its current position as a mainstream research initiative with broad applications among all divisions of science. In the first part of this series, we reviewed the structures and principles that comprise the main body of knowledge of nanoscience and nanotechnology (58). This article reviews and discusses the applications of nanotechnology to biological systems that will undoubtedly transform the foundations of disease diagnosis, treatment, and prevention in the future. Specific attention is given to developments in diagnostics and imaging at the nanoscale level. The use of nanoparticles and nanomaterials as biodetection agents for deoxyribonucleic acid and proteins is presented. In addition, nanodevices, such as nanowires, nanotubes, and nanocantilevers, can be combined with nanoarrays and nanofluidics to create integrated and automated nanodetection platforms. Molecular imaging modalities based on quantum dots and magnetic nanoparticles are also discussed. This technology has been extended to the imaging of intracranial neoplasms. Further innovation within these disciplines will form the basis for the development of mature nanomedicine. The final article of the series will focus on additional advancements in nanomedicine, namely nanotherapy and nanosurgery, and will cover the innovations that will lead to the eventual realization of nanoneurosurgery.

Surgery of the mind and mood: a mosaic of issues in time and evolution.

The prevalence and economic burden of neuropsychiatric disease are enormous. The surgical treatment of these psychiatric disorders, although potentially valuable, remains one of the most controversial subjects in medicine, as its concept and potential reality raises thorny issues of moral, ethical, and socioeconomic consequence.This article traces the roots of concept and surgical efforts in this turbulent area from prehistory to the 21st century. The details of the late 19th and 20th century evolution of approaches to the problem of intractable psychiatric diseases with scrutiny of the persona and contributions of the key individuals Gottlieb Burckhardt, John Fulton, Egas Moniz, Walter Freeman, James Watts, and William Scoville are presented as a foundation for the later, more logically refined approaches of Lars Leksell, Peter Lindstrom, Geoffrey Knight, Jean Talaraich, and Desmond Kelly. These refinements, characterized by progressive minimalism and founded on a better comprehension of underlying pathways of normal function and disease states, have been further explored with recent advances in imaging, which have allowed the emergence of less invasive and technology driven non-ablative surgical directives toward these problematical disorders of mind and mood.The application of therapies based on imaging comprehension of pathway and relay abnormalities, along with explorations of the notion of surgical minimalism, promise to serve as an impetus for revival of an active surgical effort in this key global health and socioeconomic problem.Eventual coupling of cellular and molecular biology and nanotechnology with surgical enterprise is on the horizon.

ABERRANT ANGIOGENIC CHARACTERISTICS OF HUMAN BRAIN ARTERIOVENOUS MALFORMATION ENDOTHELIAL CELLS

OBJECTIVETo identify and characterize the phenotypic and functional differences of endothelial cells derived from cerebral arteriovenous malformations (AVM), as compared with endothelial cells derived from a normal brain. METHODSIsolated AVM brain endothelial cells and control brain endothelial cells were evaluated immunohistochemically for expression of the endothelial cell markers von Willebrand factor and CD31, as well as angiogenic factors including vascular endothelial growth factor A, interleukin-8, and endothelin-1. Vascular endothelial growth factor receptors 1 and 2 were also evaluated using immunohistochemistry techniques. Functional assays evaluated cell proliferation, cytokine production, tubule formation, and cell migration using the modified Boyden chamber technique. RESULTSEndothelial cells derived from AVMs expressed high levels of vascular endothelial growth factor A and significantly overexpressed the vascular endothelial growth factor receptors 1 and 2 (P < 0.05), as compared with control endothelial cells. In addition, comparison to control brain endothelial cells demonstrated that AVM brain endothelial cells proliferated faster, migrated more quickly, and produced aberrant tubule-like structures. CONCLUSIONEndothelial cells derived from cerebral AVMs are highly activated cells overexpressing proangiogenic growth factors and exhibiting abnormal functions consistent with highly activated endothelial cells.

Man, Mind, and Machine: The Past and Future of Virtual Reality Simulation in Neurologic Surgery

OBJECTIVE To review virtual reality in neurosurgery, including the history of simulation and virtual reality and some of the current implementations; to examine some of the technical challenges involved; and to propose a potential paradigm for the development of virtual reality in neurosurgery going forward. METHODS A search was made on PubMed using key words surgical simulation, virtual reality, haptics, collision detection, and volumetric modeling to assess the current status of virtual reality in neurosurgery. Based on previous results, investigators extrapolated the possible integration of existing efforts and potential future directions. RESULTS Simulation has a rich history in surgical training, and there are numerous currently existing applications and systems that involve virtual reality. All existing applications are limited to specific task-oriented functions and typically sacrifice visual realism for real-time interactivity or vice versa, owing to numerous technical challenges in rendering a virtual space in real time, including graphic and tissue modeling, collision detection, and direction of the haptic interface. CONCLUSIONS With ongoing technical advancements in computer hardware and graphic and physical rendering, incremental or modular development of a fully immersive, multipurpose virtual reality neurosurgical simulator is feasible. The use of virtual reality in neurosurgery is predicted to change the nature of neurosurgical education, and to play an increased role in surgical rehearsal and the continuing education and credentialing of surgical practitioners.

Vagus Nerve Stimulation

Vagus nerve stimulation (VNS) is a safe and reliable treatment adjunct for patients with medically intractable epilepsy. It is both a preventive and an abortive form of therapy, potentially effective against both partial and generalized seizures in adults and children. VNS also has a number of serendipitous effects on mood, memory, and attention and has been approved for the treatment of refractory depression. Because of its pleiotropic effects, it holds promise for several other diseases as well. Its principal limitations are its unknown mechanism of action, the low likelihood of complete cure, and the inability to predict which patients will derive substantial benefit. This paper reviews the theoretical rationale, practical background, and clinical applications of VNS therapy.

Toward the Emergence of Nanoneurosurgery: Part I—Progress in Nanoscience, Nanotechnology, and the Comprehension of Events in the Mesoscale Realm

Since its original conception in 1959, the notion of nanotechnology and its potential ramifications have not only created fascination, but also intense scientific effort and scrutiny. Currently, research activities are being principally conducted in mesoscale, the realm between nanoscale and macroscale, with the rudiments of nanoscience being defined in realities and principles that will determine activities and discoveries in the future. This paper reviews and discusses the evolution of nanoscience, its contemporary status, and the discoveries that currently constitute the main components of the body of knowledge from a neurosurgical perspective. Specific attention is given to the developments in imaging, fabrication, nanostructures, nanoelectromechanical systems, molecular manufacturing, nanocomputation, and emerging physical and chemical concepts in mesoscale, as they will establish foundations for the realization of nanomedicine and nanoneurosurgery.