Connectivity in the Mammalian Brain
Last fall, an INI research team led by Michael Bienkowski, PhD, released the world’s most detailed atlas of the mouse hippocampus, a part of the brain key for memory and spatial navigation. The study, published in Nature Neuroscience, was one of the journal’s all-time most popular papers and scored in the top 1% of all research outputs tracked by Altmetric.
Now, Bienkowski’s team has released a new study in the Journal of Comparative Neurology that examines connectivity between several key parts of the mammalian visual system, including the dorsal lateral geniculate nucleus of the thalamus, the primary visual cortex and extrastriate visual cortices.
“We found new pathways in the mouse brain that relay visual signals from the eye to the cortex where conscious perception of vision occurs,” Bienkowski says. “We believe these pathways may underlie a phenomenon known as ‘blindsight’ in patients who retain some visual abilities despite a loss of vision due to brain damage.”
The Journal of Comparative Neurology’s June 2019 cover will feature a visualization of the brain that Bienkowski created (image left) with the same methods used in the study. A coronal tissue section from the mouse brain was stained using chemical markers that help researchers better understand how the brain is organized. In this image, the large magenta-stained region in the center is the thalamus; the dense green-stained region in the lower right is the hypothalamus.
Another paper from researchers at the Center for Integrative Connectomics (CIC), a part of INI dedicated to mapping connectivity and led by Hongwei Dong, MD, PhD, was published in Nature Communications in April. The team, which included Houri Hintiryan, PhD, graduate student Muye Zhu and Bienkowski, among others, created a new method of automatically segmenting individual neurons in brain tissue, called G-Cut. The new tool can assist researchers to create enhanced digital reconstructions of neurons and their circuitry.
The Blood Brain Barrier and Alzheimer’s Disease
INI’s Arthur W. Toga, PhD, and Farshid Sepehrband, PhD, teamed up with a group of researchers from across USC and beyond to study the role of the blood brain barrier in Alzheimer’s disease. The five-year investigation found that leaky capillaries that allow toxins to enter the brain are an early hallmark of Alzheimer’s. The study, which has major implications for diagnosing and treating the disease, was published in January in Nature Medicine.
The Blood Brain Barrier
Jim Stanis, INI’s medical animator, created this animation depicting the blood brain barrier's role in neurodegeneration. The blood brain barrier lines the vessels of the circulatory system in the brain, preventing harmful substances from crossing. This animation explains its anatomy at a micro level—and what happens when it starts to break down.
Evaluating a New MRI Technique
In a new study, currently in press with Magnetic Resonance in Medicine, INI’s Judy Pa, PhD, and graduate student Ashwin Sakhare evaluated the reliability of phase-contrast MRI, a noninvasive imaging method that allows researchers to measure cerebrospinal fluid (CSF) flow and cerebral blood flow (CBF). CSF and CBF play an important role in supplying the brain with oxygen and glucose, protecting it from injury and for removing waste. Disruption in these pathways has been linked to pathology such as dementia. Pa’s research indicates that phase-contrast MRI can be used to reliably test CSF and CBF flows, making it a useful technique for future research on brain health.
White Matter Diffusivity and Alzheimer’s Disease
Led by Farshid Sepehrband, PhD, a team of INI researchers used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI-3) to examine why the brains of Alzheimer’s patients tend to have higher “mean diffusivity,” or fluid diffusion levels, in white matter compared to healthy controls (image above). The study, which traced the disparity to increased fluid in lacunes and perivascular spaces, is currently in press with Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring.
“This finding has high clinical significance because it can aid in early diagnosis and disease monitoring,” Sepehrband says. “It also represents a concrete step toward understanding the pathophysiological mechanisms of Alzheimer’s disease.”
New Noninvasive Imaging Tools
INI’s Xingfeng Shao, a doctoral student who works with Danny JJ Wang, PhD, successfully defended his dissertation in March. His research, which involved creating a new algorithm and MR pulse sequence to noninvasively measure the blood brain barrier’s permeability to water, was published in Magnetic Resonance in Medicine. The findings may ultimately help in the diagnosis of cerebral small vessel disease and the cognitive impairment associated with it.
Shao also published a second article in Magnetic Resonance in Medicine along with several INI colleagues. The study builds on the institute’s ongoing work on non-contrast 4D dynamic MR angiography, a powerful method of imaging blood vessels in the brain that does not require the use of radioactive substances for contrast. By proposing a new analytical method for measuring arterial blood flow, these findings could aid in the clinical diagnosis of cerebrovascular disorders.
TRAINING AND OUTREACH
Science Fair Season
INI faculty and staff are committed to supporting students pursuing careers in the neurosciences. In March, several members of the institute, including Kay Jann, PhD, Tyler Ard, PhD, and Dominique Duncan, PhD, served as volunteer judges at the nearby Francisco Bravo Medical Magnet High School’s Annual Science and Engineering Fair.
Learn more about the event here
Later in the month, Farshid Sepehrband, PhD, and Jeiran Choupan, PhD, volunteered to judge at the 69th Annual Los Angeles County Science and Engineering Fair, where Choupan was also named chair of engineering applications for high school seniors.
INI’s student researchers also participated in science fairs this spring. Jiaju Liu and Steven Lovera, high school students who work with Dominique Duncan, PhD, on the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx), each received second place at their respective high school science fairs. Lovera’s project covered his work on post-traumatic epilepsy and imaging procedures, while Liu’s explored a novel approach to detect the development of epilepsy using a nonlinear analysis. Liu placed second at the regional Los Angeles County Science and Engineering Fair and will compete at the state level this spring.
Other Student Accomplishments
Meanwhile, INI’s Kay Jann, PhD, worked with another group of students on a new publication. Nooralhoda Sadeghi, a member of the Big Data Discovery and Diversity program and a student at California State University, Fullerton, and Brendan Angelo and Akul Sharma, INI Neuroimaging and Informatics (NIIN) master’s alumni who graduated in 2018, coauthored an abstract that used nodes to identify brain networks and was accepted to the Organization of Human Brain Mapping.
And Faisal Rashid, a student in the NIIN program who will graduate in May, was sworn in as the Los Angeles Police Department’s first officer of Bangladeshi descent through its reserve program. Rashid completed nearly two years of training while studying at USC and working in the department of radiation oncology.
“Law enforcement officers are typically first responders to emergencies that involve individuals with mental health problems, trauma, or troubled adolescents. Sometimes, the right interaction with the right people can change the trajectory of someone’s life for the better," Rashid says, adding that it’s always been a priority for him to give back to the city of Los Angeles, where he was born and raised.
Hosung Kim Receives BrightFocus Award for Alzehimer’s Disease Research
INI’s Hosung Kim, PhD, received a three-year, $300,000 award from the BrightFocus Foundation, a nonprofit that funds cures for several neurological and eye diseases. With the funding, Kim will use deep-learning modeling and multicontrast MRI databases to create an algorithm that can more accurately predict an individual’s physiological brain age. The project may help diagnose patients with mild cognitive impairment and Alzheimer’s disease using noninvasive imaging methods.
Michael Bienkowski Joins the INI Faculty
Michael Bienkowski, PhD, joined the INI faculty in January as an assistant professor of research after working at the institute as a postdoctoral researcher since 2013. Bienkowski, who completed his doctorate in neuroscience at the University of Pittsburgh, studies the relationship between anatomy, genetics and function with brain regions involved in memory and emotion.
Meet Our Featured Postdocs
Daniel Albrecht received his doctorate in medical neuroscience from the Indiana University School of Medicine. His research focuses on using multimodal neuroimaging techniques (e.g. PET, MRI) to investigate the biological substrates of neurological disease, with a particular interest in understanding how inflammation contributes to processes underlying dementia. He is also working on a project looking at the associations between decreased cerebral blood flow and aggregation of misfolded protein (i.e. amyloid, tau) throughout the progression of Alzheimer’s disease.
Christopher Ching completed his doctorate in neuroscience at UCLA, where he studied neuroimaging markers of psychiatric disorders. He now leads the Enhancing Neuro Imaging Genetics Through Meta-Analysis (ENIGMA) bipolar disorder working group, the largest neuroimaging study of bipolar disorder, which aims to identify generalizable and replicable brain markers to improve diagnosis and treatment. One of his research interests involves identifying multimodal interactions between aging, Alzheimer's disease and psychiatric risk markers, which may help predict long-term outcomes, better differentiate notoriously heterogeneous psychiatric patient populations, and identify modifiable factors for future psychiatric treatment trials.
Jin Kyu Gahm completed his doctorate in computer science at UCLA with a focus on diffusion tensor image processing. Since joining INI in 2014, he has developed cutting-edge algorithms for modeling brain shape and connectivity and applied them in large-scale brain image analyses. In particular, the theory and applications of his work on Riemannian Metric Optimization on Surface (RMOS) were reported in the top-tier journal Medical Image Analysis and at the MICCAI conference. He is currently developing a new surface-based approach for reconstructing short association fibers in the superficial white matter from diffusion MRI data.
ini in the news
Judy Pa Talks Alzheimer’s Disease with Larry King
INI’s Judy Pa, PhD, (left) will appear on the show Larry King NOW in early May. She discusses myths about Alzheimer’s disease versus normal aging, progress in tackling Alzheimer’s and current lifestyle factors that may improve brain health and reduce risk.
Mapping the Brain’s Memory Bank on the NIH Director’s Blog
Blood Test Might Yield Early Warning of Alzheimer’s from U.S. News & World Report
USC Researchers Use AI to Detect Early Signs of Alzheimer’s in Viterbi News
Learn more about Our Research
Visit us online at www.ini.usc.edu.