Virtual Reality and Robotics in Neurosurgery—Promise and Challenges

Robotic technologies have the potential to help neurosurgeons perform precise, technically demanding operations, together with virtual reality environments to help them navigate through the brain, according to a special supplement to Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

"Virtual Reality (VR) and robotics are two rapidly expanding fields with growing application within neurosurgery," according to an introductory article by Garnette Sutherland, MD. The 22 reviews, commentaries, and original studies in the special supplement provide an up-to-the-minute overview of "the benefits and ongoing challenges related to the latest incarnations of these technologies."

Robotics and VR in Neurosurgery—What’s Here and What’s Next
Virtual reality and robotic technologies present exciting opportunities for training, planning, and actual performance of neurosurgical procedures. Robotic tools under development or already in use can provide mechanical assistance, such as steadying the surgeon’s hand or “scaling” hand movements. “Current robots work in tandem with human operators to combine the advantages of human thinking with the capabilities of robots to provide data, to optimize localization on a moving subject, to operate in difficult positions, or to perform without muscle fatigue,” writes Dr. Sutherland.

Virtual reality technologies play an important role, providing “spatial orientation” between robotic instruments and the surgeon. Virtual reality environments “recreate the surgical space” in which the surgeon works, providing 3-D visual images as well as haptic (sense of touch) feedback. The ability to plan, rehearse, and “play back” operations in the brain could be particularly valuable for training neurosurgery residents—especially since recent work hour changes have limited opportunities for operating room experience.

The special supplement to Neurosurgery presents authoritative updates by experts working in the field of surgical robotics and VR technology, drawn from a wide range of disciplines. Topics include robotic technologies already in use, such as the “neuroArm” image-guided neurosurgical robot; reviews of progress in areas such as 3-D neurosurgical planning and virtual endoscopy; and new thinking on the best approaches to development, evaluation, and clinical uses of VR and robotic technologies.

But numerous and daunting technical challenges remain to be met before robotic and VR technologies become widely used in clinical neurosurgery. For example, VR environments require extremely fast processing times to provide the surgeon with continuously updated sensory information—equal to or faster than the brain’s ability to perceive it.

Economic challenges include the high costs of developing and implementing VR and robotic technologies, especially in terms of showing that the costs are justified by benefits to the patient. Continued progress in miniaturization will play an important role both in overcoming the technical challenges and in making the technology cost-effective.

The editors of Neurosurgery hope their supplement will stimulate interest and further progress in the development and practical implementation of VR and robotic technologies for neurosurgery. Dr. Sutherland adds, “Collaboration between the fields of medicine, engineering, science, and technology will allow innovations in these fields to converge in new products that will benefit patients with neurosurgical disease.”

(Image courtesy: Imperial College London)

Strange behavior: new study exposes living cells to synthetic protein

One approach to understanding components in living organisms is to attempt to create them artificially, using principles of chemistry, engineering and genetics. A suite of powerful techniques—collectively referred to as synthetic biology—have been used to produce self-replicating molecules, artificial pathways in living systems and organisms bearing synthetic genomes. 

In a new twist, John Chaput, a researcher at Arizona State University’s Biodesign Institute and colleagues at the Department of Pharmacology, Midwestern University, Glendale, AZ have fabricated an artificial protein in the laboratory and examined the surprising ways living cells respond to it. 

“If you take a protein that was created in a test tube and put it inside a cell, does it still function,” Chaput asks. “Does the cell recognize it? Does the cell just chew it up and spit it out?” This unexplored area represents a new domain for synthetic biology and may ultimately lead to the development of novel therapeutic agents. 

The research results, reported in the advanced online edition of the journal ACS Chemical Biology, describe a peculiar set of adaptations exhibited by Escherichia coli bacterial cells exposed to a synthetic protein, dubbed DX. Inside the cell, DX proteins bind with molecules of ATP, the energy source required by all biological entities.

A model-free way to characterize polymodal ion channel gating

Two studies in The Journal of General Physiology (JGP) help pave the way for a “shortcut” model-free approach to studying activation of “polymodal” ion channels—channels that open in response to multiple stimuli. Transmembrane ion channels respond to various physiological stimuli to regulate numerous cellular functions. Different classes of channels respond to different types of stimuli; some channels, for instance, respond to changes in membrane potential whereas others are activated by ligand binding. Polymodal channels integrate different cellular signals, enabling them to mediate a more precise and flexible physiological response. Understanding the mechanisms involved in polymodal channel activation has been a challenge, however, in part because of the complexity of the models required.

Now, two studies in the January issue of JGP use straightforward thermodynamically rigorous analysis to parse the free energy of polymodal voltage- and ligand-dependent ion channels.

In one study, University of Wisconsin–Madison researchers Sandipan Chowdhury and Baron Chanda examine the BK channel—a channel activated by both changes in membrane potential and calcium binding to an intracellular domain. In the second study, Daniel Sigg (dPET Professional Services) explores gating of polymodal ion channels in general. Specifically, the authors show how to use G-V (conductance-voltage), Q-V (charge-voltage) and conductance vs. ligand concentration measurements to extract the free energies of interaction of the modules of a polymodal channel that respond to these distinct modalities.

This new approach opens the door for a model-independent way to studying ion channel gating, which could be useful both for constraining future atomic-scale models of channel gating, and in understanding the disruptions that result from disease causing genetic mutations.

Chowdhury, S., and B. Chanda. 2013. J. Gen. Physiol. doi:10.1085/jgp.201210860
Sigg, D., et al. 2013. J. Gen. Physiol. doi:10.1085/jgp.201210859
Yifrach, O. 2013. J. Gen. Physiol. doi:10.1085/jgp.201210929

Investigators’ Study Hints That Stem Cells Prepare for Maturity Much Earlier Than Anticipated

Unlike less versatile muscle or nerve cells, embryonic stem cells are by definition equipped to assume any cellular role. Scientists call this flexibility “pluripotency,” meaning that as an organism develops, stem cells must be ready at a moment’s notice to activate highly diverse gene expression programs used to turn them into blood, brain, or kidney cells.

Scientists from the lab of Stowers Investigator Ali Shilatifard, Ph.D., report in the December 27, 2012 online issue of Cell that one way cells stay so plastic is by stationing a protein called Ell3 at stretches of DNA known as “enhancers” required to activate a neighboring gene. Their findings suggest that Ell3 parked at the enhancer of a developmentally regulated gene, even one that is silent, primes it for future expression. This finding is significant as many of these same genes are abnormally switched on in cancer.

“We now know that some enhancer misregulation is involved in the pathogenesis of solid and hematological malignances,” says Shilatifard. “But a problem in the field has been how to identify inactive or poised enhancer elements. Our discovery that Ell3 interacts with enhancers in ES cells gives us a hand-hold to identify and to study them.”

Brain & Behavior Research Foundation Announces 10 Major Research Achievements of 2012

In 2012, the Brain & Behavior Research Foundation funded more than 200 new promising ideas through its NARSAD Grants to identify the causes, improve treatments and develop prevention strategies for mental illness. Many research projects also came to fruition in 2012, and the Foundation highlights ten significant findings.

Monkey See, Monkey Do: Visual Feedback Is Necessary for Imitating Facial Expressions

Studies of the chameleon effect confirm what salespeople, tricksters, and Lotharios have long known: Imitating another person’s postures and expressions is an important social lubricant.

But how do we learn to imitate with any accuracy when we can’t see our own facial expressions and we can’t feel the facial expressions of others?

Richard Cook of City University London, Alan Johnston of University College London, and Cecilia Heyes of the University of Oxford investigate possible mechanisms underlying our ability to imitate in two studies published in Psychological Science, a journal of the Association for Psychological Science.

In the first experiment, the researchers videotaped participants as they recited jokes and then asked them to imitate four randomly selected facial expressions from their videos. When they achieved what they perceived to be the target expression, the participants recorded the attempt with the click of a computer mouse.

A computer program evaluated the accuracy of participants’ imitation attempts against a map of the target expression. In contrast to previous studies that relied on subjective assessments, this new technology allowed for automated and objective measurement of imitative accuracy.

In one experiment, the researchers found that participants who were able to see their imitation attempts through visual feedback improved over successive attempts. But participants who had to rely solely on proprioception – sensing the relative position of their facial features – got progressively worse.

These results are consistent with the associative sequence-learning model, which holds that our ability to imitate accurately depends on learned associations between what we see (in the mirror or through feedback from others) and what we feel.

Cook and colleagues conclude that contingent visual feedback may be a useful component of rehabilitation and skill-training programs that are designed to improve individuals’ ability to imitate facial gestures.

A New Focus on the ‘Post’ in Post-Traumatic Stress

Psychological trauma dims tens of millions of lives around the world and helps create costs of at least $42 billion a year in the United States alone. But what is trauma, exactly?

Both culturally and medically, we have long seen it as arising from a single, identifiable disruption. You witness a shattering event, or fall victim to it — and as the poet Walter de la Mare put it, “the human brain works slowly: first the blow, hours afterward the bruise.” The world returns more or less to normal, but you do not.

In 1980, the Diagnostic and Statistical Manual of Mental Disorders defined trauma as “a recognizable stressor that would evoke significant symptoms of distress in almost everyone” — universally toxic, like a poison.

But it turns out that most trauma victims — even survivors of combat, torture or concentration camps — rebound to live full, normal lives. That has given rise to a more nuanced view of trauma — less a poison than an infectious agent, a challenge that most people overcome but that may defeat those weakened by past traumas, genetics or other factors.

Now, a significant body of work suggests that even this view is too narrow — that the environment just after the event, particularly other people’s responses, may be just as crucial as the event itself.

The idea was demonstrated vividly in two presentations this fall at the Interdisciplinary Conference on Culture, Mind and Brain at the University of California, Los Angeles. Each described reframing a classic model of traumatic experience — one in lab rats, the other in child soldiers.

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