Quinnipiac University College of Arts and Sciences

Neuroscientists Get Together

In Faculty, Research on December 3, 2013 at 4:26 pm

blog_ToddSanDiego

By Todd H. Ahern, Assistant Professor of Psychology and Behavioral Neuroscience

Each fall the Society for Neuroscience (SFN) holds its annual conference. Founded in 1969, SFN boasts a domestic and international membership of 42,000 and has a four-fold mission: to advance our understanding of the brain and nervous system, assist neuroscientists in professional development, promote public awareness and understanding of neuroscientific research, and inform policymakers about how neuroscience impacts and benefits society.

Attendance at the annual conference has grown markedly over the last two decades, and this year over 30,000 scientists, teachers, students, exhibitors, and journalists converged on the Convention Center in beautiful San Diego, CA, to participate in the event. (To see just how beautiful, view my picture from lunch below.) Over 5 days, attendees took part in a dizzying array of lectures, symposia, and poster sessions addressing the remarkable breadth of neuroscience-related topics, from connectomics and optogenetic manipulation of brain circuits, to functional imaging of brain disorders and diseases, to the effects of neuroscience in the courtroom. (You can browse the offerings here.)

Thanks to travel support from CAS (the College of Arts and Science) and the University at large, Dr. Adrienne Betz and I not only attended but presented 3 of the 15,000 exhibited posters. Our posters summarized the work we and our many undergraduate and graduate students have conducted on the role of naturally occurring developmental cell death in shaping brain systems and the effects of the industrial chemical BBP (benzyl butyl phthalate) on neuronal plasticity and growth. In addition to our scientific work, we also presented a poster detailing the success of the annual NEURON (Northeast Under/graduate Research Organization for Neuroscience) Conference. The striking growth of the NEURON meeting over the last three years is due in large part to Dr. Betz’s exceptional and tireless work of hosting it here at Quinnipiac. (Note: the next meeting will be February 23rd, 2014, at the Frank H. Netter MD Medical School.)

These poster presentations allowed us to meet with colleagues, foster collaborations, discuss advances in our respective fields, and talk about the exciting changes Quinnipiac is experiencing with its growth and the opening of the new Medical School. The conference also allowed us to connect with other neuroscience-related societies, such as the Society for Behavioral Neuroendocrinology (SBN), in which I am an active member and currently the chair of the website committee, and the Faculty for Undergraduate Neuroscience (FUN), in which several QU faculty are members, including Drs. Lise Thomas and Lani Keller from Biology and Drs. Adrienne Betz  and me from Psychology.

With such a large conference, the space here would be inadequate to summarize the vast wealth of cutting edge scholarship we encountered, but it is worth reporting on one of the most exciting symposia I attended.

Deep brain stimulation (DBS) is emerging as one of the most promising treatments for patients suffering from a severe, intractable, neurological or psychiatric disorder. First used to treat debilitating cases of Parkinson’s Disease, the procedure involves patients undergoing surgery in which electrodes are lowered into an area of the brain that shows abnormal neuronal activity. For instance, to treat Parkinson’s Disease, neurosurgeons situate electrodes in the subthalamic nucleus (STN) or internal portion of the globus pallidus (GPi). The electrodes are then wired to a pacemaker-like device that is surgically implanted in the chest. Low-powered stimulation of the target brain area almost instantaneously relieves the Parkinsonian symptoms of dystonia (sustained muscle contractions that cause abnormal postures and movement) and resting tremor (e.g., a pill-rolling motion at rest).

Despite a proliferation of clinical research using DBS to treat disorders ranging from Parkinson’s Disease to Tourette’s Syndrome, to Obesity and its hypothesized use for Anorexia Nervosa, researchers have been upfront that they don’t fully understand how it works. That’s what the SFN symposium on the Mechanisms of Deep Brain Stimulation Efficacy in Neuropsychiatric Disorders aimed to start addressing.

The first speaker was Dr. Kendall Lee, an MD/PhD neurosurgeon at the Mayo Clinic with a close engineering collaboration. Dr. Lee began his talk by describing the Wireless Intracranial Neurotransmitter Sensor (WINCS) device that his team designed and used to detect neurotransmitter release within brain areas in near real-time (e.g., dopamine release in the STN or GPi). In recent years, they’ve extended this technology to create a self-contained system that simultaneously records and wirelessly transmits information about local electrical activity and neurotransmitter release, which is then analyzed in real-time, and can then cause the same unit to provide the appropriate level of electrode stimulation. Such a closed-loop system (which they’ve dubbed the HARMONI circuit) is tiny, robust, and shows the potential to therapeutically treat pharmacologically intractable cases of Parkinson’s, Obsessive Compulsive Disorder (OCD), Tourette’s, and even memory deficits, while at the same time collecting enormous amounts of data about how DBS is working within the brain. Dr. Lee also envisions this technology as a potential treatment for para- and quadriplegics. Nerve tissue within the spinal cord isn’t able to regenerate across the severed portion of the cord after damage; there are, however, still nerves on each side. If HARMONI can be implanted on the upper-side of the injury and an electrode array below, the technology may be able to wirelessly “jump” over the injury so that signals coming from the brain can still stimulate nerves below the point of damage, allowing the recovery of coordinated movement.

Dr. Lee’s talk was followed by Dr. Cameron McIntyre (of Case Western Reserve University) and his description of new computer modeling approaches to understanding DBS. Using high resolution (diffusion tensor imaging) brain scans of the fiber-tracts that connect different parts of the brain of over a dozen DBS patients, Dr. McIntyre is starting to tease apart which fiber-tracts need to be stimulated in order to consistently produce strong therapeutic effects. This work is necessary so DBS can move into clinical trials, in which small adjustments on a patient-by-patient basis are not possible. Therefore, the use of big data analysis may allow researchers and clinicians to distinguish why some patients respond almost perfectly while others show a more modest improvement despite nearly identical electrode placement. Such precision is not trivial. Drs. Helen Mayberg and McIntyre found that mere millimeter differences in stimulation can have a dramatic effect.

In the case of DBS for major depression, electrodes are placed in the subgenual anterior cingulate cortex near the front of the brain and each electrode has several contact points, each 1-2 millimeters higher or lower than the next one. In patients with severe intractable depression (in which patients describe “a kind of stickiness,” “paralysis,” a feeling of being lost to themselves, and a “feeling like sliding down into the bottom of a well with no one there”), the researchers found that stimulation at one contact point can produce complete remission of depression, while a contact point 1-2 millimeters higher might have no effect at all or even make the depression worse. Such minute differences helped to explain why some patients responded and some responded minimally, and illustrates the need to more fully understand how DBS works before it is used more generally.

The promise, however, is striking. Based on Dr. Mayberg’s remarkable series of studies, severely depressed patients are now self-reporting a “sense of calm, quiet relief,” a “resolution of pain [and] dread,” and a renewed “interest, energy, and awareness.” The researchers have even measured positive physiological changes in galvanic skin conductance and heart rate. Importantly, the treatment is not creating an artificial happiness or the equivalent of a drug-induced high. In fact, the one patient that did find the stimulation pleasurable found the DBS therapeutically ineffective until the electrodes were moved to a different location that no longer induced pleasure. Instead, DBS seems to be freeing the patients to be themselves – something that therapy and pharmacological interventions had failed to accomplish in these patients.

As one sees these results, one cannot help but be impressed. But there is also a lingering sense of danger. As with the incredible rise of pharmacological treatments for many disorders, the opportunity for abuse is likely to grow along with its growing therapeutic use (e.g., Adderall). We’ll have to wait and see…

While not every session or poster at SFN was quite as stimulating (yes, pun intended), I did attend some other fascinating talks, including one by Tracy Bale (UPenn) on transgenerational epigenetic transmission of behavioral and physiological traits in a sex-dependent manner (e.g., parenting behavior, anxiety, and obesity); another by Jeff Lichtman (Harvard) on the push to create a connectomic (wiring diagram) map of the human nervous system using high-throughput ultra-thin tissue sectioning, electron microscopy (EM), and automated analysis of EM images; and another by Eve Marder (Brandeis) on the limits of connectomics, since having the “wiring diagram” only tells part of the functional picture. These experiences were complemented by my time at a panel discussion on the new BRAIN initiative (and the European Human Brain Project) as well as a symposium on the status of paper textbooks in relation to the many electronic offerings. (Summary: most of the speakers, who are themselves on the bleeding edge of electronic alternatives to textbooks, do not see the bound textbook going away. One of the speakers presented research demonstrating the downsides to e-text alternatives, such as e-reading requiring more time, inducing more fatigue, and being less accessible in many circumstances.)

In the end, the trip to San Diego was not only a nice change in weather (~72F versus the cold snap in CT), a great opportunity to present our work and the work of our students, but an intellectually stimulating endeavor that has already spilled over into the classroom. We were already scheduled to discuss DBS this week in class and the students seemed keen to know more. I was thrilled to have more to tell them.

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