Category: Uncategorized

A focused approach to imaging neural activity in the brain

Anne Trafton |

When neurons fire an electrical impulse, they also experience a surge of calcium ions. By measuring those surges, researchers can indirectly monitor neuron activity, helping them to study the role of individual neurons in many different brain functions.

One drawback to this technique is the crosstalk generated by the axons and dendrites that extend from neighboring neurons, which makes it harder to get a distinctive signal from the neuron being studied. MIT engineers have now developed a way to overcome that issue, by creating calcium indicators, or sensors, that accumulate only in the body of a neuron.

“People are using calcium indicators for monitoring neural activity in many parts of the brain,” says Edward Boyden, the Y. Eva Tan Professor in Neurotechnology and a professor of biological engineering and of brain and cognitive sciences at MIT. “Now they can get better results, obtaining more accurate neural recordings that are less contaminated by crosstalk.”

To achieve this, the researchers fused a commonly used calcium indicator called GCaMP to a short peptide that targets it to the cell body. The new molecule, which the researchers call SomaGCaMP, can be easily incorporated into existing workflows for calcium imaging, the researchers say.

Boyden is the senior author of the study, which appears today in Neuron. The paper’s lead authors are Research Scientist Or Shemesh, postdoc Changyang Linghu, and former postdoc Kiryl Piatkevich.

Molecular focus

The GCaMP calcium indicator consists of a fluorescent protein attached to a calcium-binding protein called calmodulin, and a calmodulin-binding protein called M13 peptide. GCaMP fluoresces when it binds to calcium ions in the brain, allowing researchers to indirectly measure neuron activity.

“Calcium is easy to image, because it goes from a very low concentration inside the cell to a very high concentration when a neuron is active,” says Boyden, who is also a member of MIT’s McGovern Institute for Brain Research, Media Lab, and Koch Institute for Integrative Cancer Research.

The simplest way to detect these fluorescent signals is with a type of imaging called one-photon microscopy. This is a relatively inexpensive technique that can image large brain samples at high speed, but the downside is that it picks up crosstalk between neighboring neurons. GCaMP goes into all parts of a neuron, so signals from the axons of one neuron can appear as if they are coming from the cell body of a neighbor, making the signal less accurate.

A more expensive technique called two-photon microscopy can partly overcome this by focusing light very narrowly onto individual neurons, but this approach requires specialized equipment and is also slower.

Boyden’s lab decided to take a different approach, by modifying the indicator itself, rather than the imaging equipment.

“We thought, rather than optically focusing light, what if we molecularly focused the indicator?” he says. “A lot of people use hardware, such as two-photon microscopes, to clean up the imaging. We’re trying to build a molecular version of what other people do with hardware.”

In a related paper that was published last year, Boyden and his colleagues used a similar approach to reduce crosstalk between fluorescent probes that directly image neurons’ membrane voltage. In parallel, they decided to try a similar approach with calcium imaging, which is a much more widely used technique.

To target GCaMP exclusively to cell bodies of neurons, the researchers tried fusing GCaMP to many different proteins. They explored two types of candidates — naturally occurring proteins that are known to accumulate in the cell body, and human-designed peptides — working with MIT biology Professor Amy Keating, who is also an author of the paper. These synthetic proteins are coiled-coil proteins, which have a distinctive structure in which multiple helices of the proteins coil together.

Less crosstalk

The researchers screened about 30 candidates in neurons grown in lab dishes, and then chose two — one artificial coiled-coil and one naturally occurring peptide — to test in animals. Working with Misha Ahrens, who studies zebrafish at the Janelia Research Campus, they found that both proteins offered significant improvements over the original version of GCaMP. The signal-to-noise ratio — a measure of the strength of the signal compared to background activity — went up, and activity between adjacent neurons showed reduced correlation.

In studies of mice, performed in the lab of Xue Han at Boston University, the researchers also found that the new indicators reduced the correlations between activity of neighboring neurons. Additional studies using a miniature microscope (called a microendoscope), performed in the lab of Kay Tye at the Salk Institute for Biological Studies, revealed a significant increase in signal-to-noise ratio with the new indicators.

“Our new indicator makes the signals more accurate. This suggests that the signals that people are measuring with regular GCaMP could include crosstalk,” Boyden says. “There’s the possibility of artifactual synchrony between the cells.”

In all of the animal studies, they found that the artificial, coiled-coil protein produced a brighter signal than the naturally occurring peptide that they tested. Boyden says it’s unclear why the coiled-coil proteins work so well, but one possibility is that they bind to each other, making them less likely to travel very far within the cell.

Boyden hopes to use the new molecules to try to image the entire brains of small animals such as worms and fish, and his lab is also making the new indicators available to any researchers who want to use them.

“It should be very easy to implement, and in fact many groups are already using it,” Boyden says. “They can just use the regular microscopes that they already are using for calcium imaging, but instead of using the regular GCaMP molecule, they can substitute our new version.”

The research was primarily funded by the National Institute of Mental Health and the National Institute of Drug Abuse, as well as a Director’s Pioneer Award from the National Institutes of Health, and by Lisa Yang, John Doerr, the HHMI-Simons Faculty Scholars Program, and the Human Frontier Science Program.

COMMANDing drug delivery

by Sabbi Lall |

While we are starting to get a handle on drugs and therapeutics that might to help alleviate brain disorders, efficient delivery remains a roadblock to tackling these devastating diseases. Research from the Graybiel, Cima, and Langer labs now uses a computational approach, one that accounts for the irregular shape of the target brain region, to deliver drugs effectively and specifically.

“Identifying therapeutic molecules that can treat neural disorders is just the first step,” says McGovern Investigator Ann Graybiel.

“There is still a formidable challenge when it comes to precisely delivering the therapeutic to the cells most affected in the disorder,” explains Graybiel, an MIT Institute Professor and a senior author on the paper. “Because the brain is so structurally complex, and subregions are irregular in shape, new delivery approaches are urgently needed.”

Fine targeting

Brain disorders often arise from dysfunction in specific regions. Parkinson’s disease, for example, arise from loss of neurons in a specific forebrain region, the striatum. Targeting such structures is a major therapeutic goal, and demands both overcoming the blood brain barrier, while also being specific to the structures affected by the disorder.

Such targeted therapy can potentially be achieved using intracerebral catheters. While this is a more specific form of delivery compared to systemic administration of a drug through the bloodstream, many brain regions are irregular in shape. This means that delivery throughout a specific brain region using a single catheter, while also limiting the spread of a given drug beyond the targeted area, is difficult. Indeed, intracerebral delivery of promising therapeutics has not led to the desired long-term alleviation of disorders.

“Accurate delivery of drugs to reach these targets is really important to ensure optimal efficacy and avoid off-target adverse effects. Our new system, called COMMAND, determines how best to dose targets,” says Michael Cima, senior author on the study and the David H. Koch Professor of Engineering in the Department of Materials Science and Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research.

3D renderings of simulated multi-bolus delivery to various brain structures (striatum, amygdala, substantia nigra, and hippocampus) with one to four boluses.

COMMAND response

In the case of Parkinson’s disease, implants are available that limit symptoms, but these are only effective in a subset of patients. There are, however, a number of promising potential therapeutic treatments, such as GDNF administration, where long-term, precise delivery is needed to move the therapy forward.

The Graybiel, Cima, and Langer labs developed COMMAND (computational mapping algorithms for neural drug delivery) that helps to target a drug to a specific brain region at multiple sites (multi-bolus delivery).

“Many clinical trials are believed to have failed due to poor drug distribution following intracerebral injection,” explained Khalil Ramadi, PhD ’19, one of the lead researchers on the paper, and a postdoctoral fellow at the Koch and McGovern Institute. “We rationalized that both research experiments and clinical therapies would benefit from computationally optimized infusion, to enable greater consistency across groups and studies, as well as more efficacious therapeutic delivery.”

The COMMAND system finds balance between the twin challenges of drug delivery by maximizing on-target and minimizing off-target delivery. COMMAND is essentially an algorithm that minimizes an error that reflects leakage beyond the bounds of a specific target area, in this case the striatum. A second error is also minimized, and this encapsulates the need to target across this irregularly shaped brain region. The strategy to overcome this is to deliver multiple “boluses” to different areas of the striatum to target this region precisely, yet completely.

“COMMAND applies a simple principle when determining where to place the drug: Maximize the amount of drug falling within the target brain structure and minimize tissues exposed beyond the target region,” explains Ashvin Bashyam, PhD ’19, co-lead author and a former graduate student with Michael Cima at MIT. “This balance is specified based drug properties such as minimum effective therapeutic concentration, toxicity, and diffusivity within brain tissue.”

The number of drug sites applied is kept as low as possible, keeping surgery simple while still providing enough flexibility to cover the target region. In computational simulations, the researchers were able to deliver drugs to compact brain structures, such as the striatum and amygdala, but also broader and more irregular regions, such as hippocampus.

To examine the spatiotemporal dynamics of actual delivery, the researchers used positron emission tomography (PET) and a ‘labeled’ solution, Cu-64, that allowed them to image and follow an infused bolus after delivery with a microprobe. Using this system, the researchers successfully used PET to validate the accuracy of multi-bolus delivery to the rat striatum and its coverage as guided by COMMAND.

“We anticipate that COMMAND can improve researchers’ ability to precisely target brain structures to better understand their function, and become a platform to standardize methods across neuroscience experiments,” explains Graybiel. “Beyond the lab, we hope COMMAND will lay the foundation to help bring multifocal, chronic drug delivery to patients.”

Universal musical harmony

by Sabbi Lall |

Many forms of Western music make use of harmony, or the sound created by certain pairs of notes. A longstanding question is why some combinations of notes are perceived as pleasant while others sound jarring to the ear. Are the combinations we favor a universal phenomenon? Or are they specific to Western culture?

Through intrepid research trips to the remote Bolivian rainforest, the McDermott lab at the McGovern Institute has found that aspects of the perception of note combinations may be universal, even though the aesthetic evaluation of note combination as pleasant or unpleasant is culture-specific.

“Our work has suggested some universal features of perception that may shape musical behavior around the world,” says McGovern Associate Investigator Josh McDermott, senior author of the Nature Communications study. “But it also indicates the rich interplay with cultural influences that give rise to the experience of music.”

Remote learning

Questions about the universality of musical perception are difficult to answer, in part because of the challenge in finding people with little exposure to Western music. McDermott, who is also an associate professor in MIT’s Department of Brain and Cognitive Sciences and an investigator in the Center for Brains Minds and Machines, has found a way to address this problem. His lab has performed a series of studies with the participation of an indigenous population, the Tsimane’, who live in relative isolation from Western culture and have had little exposure to Western music. Accessing the Tsimane’ villages is challenging, as they are scattered throughout the rainforest and only reachable during the dry part of the year.

Left to right Josh McDermott (in vehicle), Alex Durango, Sophie Dolan and Malinda McPherson experiencing a travel delay en route to a Tsimane’ village after a heavy rainfall. Photo: Malinda McPherson

“When we enter a village there is always a crowd of curious children to greet us,” says Malinda McPherson, a graduate student in the lab and lead author of the study. “Tsimane’ are friendly and welcoming, and we have visited some villages several times, so now many people recognize us.”

In a study published in 2019, McDermott’s team found evidence that the brain’s ability to detect musical octaves is not universal, but is gained through cultural experience. And in 2016 they published findings suggesting that the preference for consonance over dissonance is culture-specific. In their new study, the team decided to explore whether aspects of the perception of consonance and dissonance might nonetheless be universally present across cultures.

Music lessons

In Western music, harmony is the sound of two or more notes heard simultaneously. Think of the Leonard Cohen song, Hallelujah, where he sings about harmony (“the fourth, the fifth, the minor fall and the major lift”). A combination of two notes is called an interval, and intervals that are perceived to be the most pleasant (or consonant, like the fourth and the fifth, for example) to the Western ear are generally represented by smaller integer ratios.

Intervals that are related by low integer ratios have fascinated scientists for centuries.

“Such intervals are central to Western music, but are also believed to be a common feature of many musical systems around the world,” McPherson explains. “So intervals are a natural target for cross-cultural research, which can help identify aspects of perception that are and aren’t independent of cultural experience.”

Scientists have been drawn to low integer ratios in music in part because they relate to the frequencies in voices and many instruments, known as ‘overtones’. Overtones from sounds like voices form a particular pattern known as the harmonic series. As it happens, the combination of two concurrent notes related by a low integer ratio partially reproduces this pattern. Because the brain presumably evolved to represent natural sounds, such as voices, it has seemed plausible that intervals with low integer ratios might have special perceptual status across cultures.

Since the Tsimane’ do not generally sing or play music together, meaning they have not been trained to hear or sing in harmony, McPherson and her colleagues were presented with a unique opportunity to explore whether there is anything universal about the perception of musical intervals.

Taking notes

In order to probe the perception of musical intervals, McDermott and colleagues took advantage of the fact that ears accustomed to Western musical harmony often have difficulty picking apart two “consonant” notes when they are played at the same time. This auditory confusion is known as “fusion” in the field. By contrast, two “dissonant” notes are easier to hear as separate.

The tendency of “consonant” notes to be heard by Westerners as fused could reflect their common occurrence in Western music. But it could also be driven by the resemblance of low-integer-ratio note combinations to the harmonic series. This similarity of consonant intervals to the acoustic structure of typical natural sounds raises the possibility that the human brain is biologically tuned to “fuse” consonant notes.

Graduate student and lead author, Malinda McPherson, works with a participant and translator in the field. Photo: Malinda McPherson

To explore this question, the team ran identical sets of experiments on two participant groups: US non-musicians residing in the Boston metropolitan area and Tsimane’ residing in villages in the Amazon rain forest. Listeners heard two concurrent notes separated by a particular musical interval (consonant or dissonant), and were asked to judge whether they heard one or two sounds. The experiment was performed with both synthetic and natural sounds.

They found that like the Boston cohort, the Tsimane’ were more likely to mistake two notes as a single sound if they were consonant than if they were dissonant.

“I was surprised by how similar some of the results in Tsimane’ participants were to those in US participants,” says McPherson, “particularly given the striking differences that we consistently see in preferences for musical intervals.”

When it came to whether consonant intervals were more pleasant than dissonant intervals, the results told a very different story. While the US study participants found consonant intervals more pleasant than dissonant intervals, the Tsimane’ showed no preference, implying that our sense of what is pleasant is shaped by culture.

“The fusion results provide an example of a perceptual effect that could influence musical systems, for instance by creating a natural perceptual contrast to exploit,” explains McDermott. “Hopefully our work helps to show how one can conduct rigorous perceptual experiments in the field and learn things that would be hidden if we didn’t consider populations in other parts of the world.”

Turning lemons into lemonade

by Gayle Lutchen |

When it was announced that all non-research staff were to work from home I think we were all in shock – well, I was in shock.

I always envisioned my role as being tied to actually being on campus in our building.  That said, our headquarters packed up in record time and in one day we were all working from home.  I thrive on a lot of structure in my day, so coordinated a daily check-in meeting with our HQ team. I think that has made a big difference in how we have all acclimated to working at home.

We are still connected, troubleshooting issues, and being incredibly productive.

I spent the first month basically coordinating the ramp-down of the building, so many lists!  Now thankfully, we are looking to the future, and to one day re-engaging with the building.

I see myself as a conduit for information from senior leadership at MIT to our group in MIBR HQ and I continue to brainstorm with staff, gather each morning for coffee, and put forth a glass half-full mentality.  The team I work with is amazing and I feel we keep each other focused and committed to supporting our researchers and faculty, and keeping our cool under challenging circumstances. I’ve also kept up with my workout routine and have started experimenting with different recipes for my family.  I continue to try to turn lemons into lemonade, both at work and home.

Gayle Lutchen has been the Assistant Director for Administration at the McGovern Institute for twenty years. 

#WeAreMcGovern

SHERLOCK-based one-step test provides rapid and sensitive COVID-19 detection 

by Sabbi Lall |

A team of researchers at the McGovern Institute for Brain Research at MIT, the Broad Institute of MIT and Harvard, the Ragon Institute, and the Howard Hughes Medical Institute (HHMI) has developed a new diagnostics platform called STOP (SHERLOCK Testing in One Pot) COVID. The test can be run in an hour as a single-step reaction with minimal handling, advancing the CRISPR-based SHERLOCK diagnostic technology closer to a point-of-care or at-home testing tool. The test has not been reviewed or approved by the FDA and is currently for research purposes only.

The team began developing tests for COVID-19 in January after learning about the emergence of a new virus which has challenged the healthcare system in China. The first version of the team’s SHERLOCK-based COVID-19 diagnostics system is already being used in hospitals in Thailand to help screen patients for COVID-19 infection.

The ability to test for COVID-19 at home, or even in pharmacies or places of employment, could be a game-changer for getting people safely back to work and into their communities.

The new test is named “STOPCovid” and is based on the STOP platform. In research it has been shown to enable rapid, accurate, and highly sensitive detection of the COVID-19 virus SARS-CoV-2 with a simple protocol that requires minimal training and uses simple, readily-available equipment, such as test tubes and water baths. STOPCovid has been validated in research settings using nasopharyngeal swabs from patients diagnosed with COVID-19. It has also been tested successfully in saliva samples to which SARS-CoV-2 RNA has been added as a proof-of-principle.

The team is posting the open protocol today on a new website, STOPCovid.science. It is being made openly available in line with the COVID-19 Technology Access Framework organized by Harvard, MIT, and Stanford. The Framework sets a model by which critically important technologies that may help prevent, diagnose, or treat COVID-19 infections may be deployed for the greatest public benefit without delay.

There is an urgent need for widespread, accurate COVID-19 testing to rapidly detect new cases, ideally without the need for specialized lab equipment. Such testing would enable early detection of new infections and drive effective “test-trace-isolate” measures to quickly contain new outbreaks. However, current testing capacity is limited by a combination of requirements for complex procedures and laboratory instrumentation and dependence on limited supplies. STOPCovid can be performed without RNA extraction, and while all patient tests have been performed with samples from nasopharyngeal swabs, preliminary experiments suggest that eventually swabs may not be necessary. Removing these barriers could help enable broad distribution.

“The ability to test for COVID-19 at home, or even in pharmacies or places of employment, could be a game-changer for getting people safely back to work and into their communities,” says Feng Zhang, a co-inventor of the CRISPR genome editing technology, an investigator at the McGovern Institute and HHMI, and a core member at the Broad Institute. “Creating a point-of-care tool is a critically important goal to allow timely decisions for protecting patients and those around them.”

To meet this need, Zhang, McGovern Fellows Omar Abudayyeh and Jonathan Gootenberg, and colleagues initiated a push to develop STOPCovid. They are sharing their findings and packaging reagents so other research teams can rapidly follow up with additional testing or development. The group is also sharing data on the StopCOVID.science website and via a submitted preprint. The website is also a hub where the public can find the latest information on the team’s developments.

McGovern Institute Fellows Jonathan Gootenberg (far left) Omar Abudayyeh and have developed a CRISPR research tool to detect COVID-19 with McGovern Investigator Feng Zhang (far right).
Credit: Justin Knight

How it works

The STOPCovid test combines CRISPR enzymes, programmed to recognize signatures of the SARS-CoV-2 virus, with complementary amplification reagents. This combination allows detection of as few as 100 copies of SARS-CoV-2 virus in a sample. As a result, the STOPCovid test allows for rapid, accurate, and highly sensitive detection of COVID-19 that can be conducted outside clinical laboratory settings.

STOPCovid has been tested on patient nasopharyngeal swab in parallel with clinically-validated tests. In these head-to-head comparisons, STOPCovid detected infection with 97% sensitivity and 100% specificity. Results appear on an easy-to-read strip that is akin to a pregnancy test, in the absence of any expensive or specialized lab equipment. Moreover, the researchers spiked mock SARS-CoV-2 genomes into healthy saliva samples and showed that STOPCovid is capable of sensitive detection from saliva, which would obviate the need for swabs in short supply and potentially make sampling much easier.

“The test aims to ultimately be simple enough that anyone can operate it in low-resource settings, including in clinics, pharmacies, or workplaces, and it could potentially even be put into a turn-key format for use at home,” says Abudayyeh.

Gootenberg adds, “Since STOPCovid can work in less than an hour and does not require any specialized equipment, and if our preliminary results from testing synthetic virus in saliva bear out in patient samples, it could address the need for scalable testing to reopen our society.”

The STOPCovid team during a recent zoom meeting. Image: Omar Abudayyeh

Importantly, the full test — both the viral genome amplification and subsequent detection — can be completed in a single reaction, as outlined on the website, from swabs or saliva. To engineer this, the team tested a number of CRISPR enzymes to find one that works well at the same temperature needed by the enzymes that perform the amplification. Zhang, Abudayyeh, Gootenberg and their teams, including graduate students Julia Joung and Alim Ladha, settled on a protein called AapCas12b, a CRISPR protein from the bacterium Alicyclobacillus acidophilus, responsible for the “off” taste associated with spoiled orange juice. With AapCas12b, the team was able to develop a test that can be performed at a constant temperature and does not require opening tubes midway through the process, a step that often leads to contamination and unreliable test results.

Information sharing and next steps

The team has prepared reagents for 10,000 tests to share with scientists and clinical collaborators for free around the world who want to evaluate the STOPCovid test for potential diagnostic use, and they have set up a website to share the latest data and updates with the scientific and clinical community. Kits and reagents can also be requested via a form on the website.

Acknowledgments: Patient samples were provided by Keith Jerome, Alex Greninger, Robert Bruneau, Mee-li W. Huang, Nam G. Kim, Xu Yu, Jonathan Li, and Bruce Walker. This work was supported by the Patrick J. McGovern Foundation and the McGovern Institute for Brain Research. F.Z is also supported by the NIH (1R01- MH110049 and 1DP1-HL141201 grants); Mathers Foundation; the Howard Hughes Medical Institute; Open Philanthropy Project; J. and P. Poitras; and R. Metcalfe.

Declaration of conflicts of interest: F.Z., O.O.A., J.S.G., J.J., and A.L. are inventors on patent applications related to this technology filed by the Broad Institute, with the specific aim of ensuring this technology can be made freely, widely, and rapidly available for research and deployment. O.O.A., J.S.G., and F.Z. are co-founders, scientific advisors, and hold equity interests in Sherlock Biosciences, Inc. F.Z. is also a co-founder of Editas Medicine, Beam Therapeutics, Pairwise Plants, and Arbor Biotechnologies.

Optogenetics with SOUL

by Sabbi Lall |

Optogenetics has revolutionized neurobiology, allowing researchers to use light to activate or deactivate neurons that are genetically modified to express a light-sensitive channel. This ability to manipulate neuron activity has allowed causal testing of the function of specific neurons, and also has therapeutic potential to reduce symptoms in brain disorders. However, activating neurons deep within a given brain, especially a large primate brain but even a small mouse brain, is challenging and currently requires implanting fibers that could cause damage or inflammation.

McGovern Investigator Guoping Feng and colleagues have now overcome this challenge, developing optogenetic tools that allow non-invasive stimulation of neurons in the deep brain.

“Neuroscientists have dreamed of methods to turn neurons on and off, to understand the function of different neurons, but also to repair brain malfunctions that lead to psychiatric disorders, and optogenetics made this possible” explained Feng, the James W. (1963) and Patricia T. Poitras Professor in Brain and Cognitive Sciences. “We were trying to improve the light sensitivity of optogenetic tools to broaden applications.”

Engineering with light

In order to stimulate neurons with minimal invasiveness, Feng and colleagues engineered a new type of opsin. The original breakthrough optogenetics protocol used channelrhodopsin, a light-sensitive channel discovered in algae. By expressing this channel in neurons, light of the right wavelength can be used to activate the neuron in a dish or in vivo. However, in vivo application requires the implantation of optical fibers to deliver the light close to the specific brain region being stimulated, especially if the target region is in the deep brain. In addition, if the neuron being targeted is in the deep brain, it is hard for light to reach the region in the absence of invasive tools that can damage tissue and impact the behavior of the animal.

Our study creates a method that can activate any mouse brain region, independent of its location, non-invasively.

“Prior to our study, a few studies have contributed in various ways to the development of optogenetic stimulation methods that would be minimally invasive to the brain. However, all of these studies had various limitations in the extent of brain regions they could activate,” said co-senior study author Robert Desimone, director of the McGovern Institute and the Doris and Don Berkey Professor of Neuroscience at MIT.

Probing the brain with SOUL

Feng and colleagues turned instead to new opsins, in particular SOUL, a new type of opsin that is very sensitive to even low-level light. The Feng group engineered this opsin, based on SSFO a second generation optogenetics tool, to have increased light sensitivity, and took advantage of a second property: that SOUL is activated in multiple steps, and once activated, it stays active for longer than other commonly used opsins. This means that a burst of a few seconds of low-level light can cause neurons to stay active for 10-30 minutes.

In order to put SOUL through its paces, the Feng lab expressed this channel in the lateral hypothalamus of the mouse brain. This is a deep region, challenging to reach with light, but with neurons that have clear functions that will lead to changes in behavior. Feng’s group was able to turn on this region non-invasively with light from outside the skull, and cause changes in feeding behavior.

“We were really surprised that SOUL was able to activate one of the deepest areas in the mouse brain, the lateral hypothalamus, which is 6 mm deep,” explains Feng.

But there were more surprises. When the authors activated a region of the primate brain using SOUL, they saw oscillations, waves of synchronized neuronal activity coming together like a choir. Such waves are believed to be important for many brain functions, and this result suggests that the new opsin can manipulate these brain waves, allowing scientists to study their role in the brain.

The authors are planning to move the study in several directions, studying models of brain disorders to identify circuits that may be suitable targets for therapy, as well as moving the methodology so that it can be used beyond the superficial cortex in larger animals. While it is too early to discuss applying the system to humans, the research brings us one step closer to future treatment of neurological disorders.

Family members unite to fight COVID-19

by Sugandha Sharma |

Even before MIT sent out its first official announcement about the COVID-19 crisis, I had already asked permission from my supervisor and taken my computer home so that I could start working from home.

My first and foremost concern was my family and friends. I was born and brought up in India, and then immigrated to Canada, so I have a big and wonderful family spread across both those countries. These countries had a lower number of COVID-19 cases at the time, but I could see what would be coming their way. I was anxious, very anxious. In India, my dad being an anesthetist could be exposed while working in the hospital. In Canada, my uncle who is a physician could be exposed, and on top of that he lives in the same house as my grandparents who are even more vulnerable due to their age. I knew I had to do something.

We started having regular video calls as a family. My mom even led daily online yoga sessions, and the discussions that followed those sessions ensured that we didn’t feel lonely and gave us a sense of purpose. Together, we looked at the statistics in the data from China and Italy, and learned that we needed to flatten the curve due to the lack of medical resources required to meet the need of the hour. We could foresee that more infections would lead to more patients, thus raising the demand for medical resources beyond the amount we had available.

We had several discussions around developing products for helping medical professionals and the general public during this pandemic.

We learned that since no government has enough resources to cope at the time of pandemics, we have to be innovative in trying to make the best use of the limited resources available to us.

Through our discussions and experiences of some of us in the field, we came to the conclusion that the only way to effectively fight COVID-19 is prevention at source. Hence, we started working on a mobile app that uses AI and advanced data analytics to trace contact, determine the risk of infection, and thereby suggest precautions. Luckily we have engineers and computer scientists in our family (my own background is in electrical engineering), so it was easy for us to divide the work.  In our prototype, when people sign-up, they are asked to fill out a short self-assessment form that can be used to identify any symptoms of COVID-19. This data is then used to predict vulnerable areas and to give recommendations to people who might have taken a certain route as shown below.

Sharma’s mobile app showing heatmap of the vulnerable areas in a locality in Toronto, ON (left) and personalized recommendations based on the most recent route taken by an individual (right).

We ended up submitting our proposal and prototype to the COVID-19 challenge launched by Vale (a global mining company) and the winners will be announced in May.

Personally, to be completely honest, I had my times when I broke down due to everything that was going on in the world around me. It’s not easy to see people dying, and losing jobs. My way of staying strong was to make sure that I was doing my best to contribute.

I have set up a beautiful home office for myself and I am focusing on my PhD research, being grateful that I can still continue to do it from home. I have also restarted the joint MIT-Harvard computational neuroscience journal club meetings online, so that members can get access to this wonderful community once again! It was amazing to see from a poll we conducted that 92% of the members of the club wanted the meetings to be re-started online.

These times are unprecedented for my generation, my mom’s generation and even for my grandmother’s generation. I have never seen the world come together in a way I have seen during this pandemic. The kind of response we have seen from our societies and governments across the globe shows that we can make intelligent decisions for the collective good of humanity. For once, we’re all on the same side!

Sugandha (Su) Sharma is a graduate student in the labs of Ila Fiete and Josh Tenenbaum. When she’s not developing a mobile app to fight COVID-19, Su explores the computational and theoretical principles underlying higher level cognition and intelligence in the human brain.

#WeAreMcGovern

Saxe Lab examines social impact of COVID-19

by Julie Pryor |

After being forced to relocate from their MIT dorms during the COVID19 crisis, two members of the Saxe lab are now applying their psychology skills to study the impact of mandatory relocation and social isolation on mental health.

“When ‘social distancing’ measures hit MIT, we tried to process how the implementation of these policies would impact the landscape of our social lives,” explains graduate student Heather Kosakowski, who conceived of the study late one evening with undergraduate Michelle Hung.  This landscape is broad, examining the effects of being uprooted and physically relocated from a place, but also changes in social connections, including friendships and even dating life.

MIT undergrad Michelle Hung in the Saxe lab. Photo: Michelle Hung

“I started speculating about how my life and the lives of other MIT students would change,” says Hung. “I was overwhelmed, sad, and scared. But then we realized that we were actually equipped to find the answers to our questions by conducting a study.”

Together, Kosakowski and Hung developed a survey to measure how the social behavior of MIT students, postdocs, and staff is changing over the course of the pandemic. Survey questions were designed to measure loneliness and other aspects of mental health. The survey was sent to members of the MIT community and shared on social media in mid-March, when the pandemic hit the US, and MIT made the unprecedented decision to send students home, shift to online instruction, and dramatically ramp down operations on campus.

More than 500 people responded to the initial survey, ranging in age from 18 to 60, living in cities and countries around the world. Many but not all of those who responded were affiliated with MIT. Kosakowski and Hung are sending follow-up surveys to participants every two weeks and the team plans to collect data for the duration of the pandemic.

“Throwing myself into creating the survey was a way to cope with feeling sad about leaving a community I love,” explains Hung, who flew home to California in March and admits that she struggles with feelings of loneliness now that she’s off campus.

Although it is too soon to form any conclusions about their research, Hung predicts that feelings of loneliness may actually diminish over the course of the pandemic.

“Humans have an impressive ability to adapt to change,” she says. “And I think in this virtual world, people will find novel ways to stay connected that we couldn’t have predicted.”

Whether we find ourselves feeling more or less lonely as this COVID-19 crisis comes to an end, both Kosakowski and Hung agree that it will fundamentally change life as we know it.

The Saxe lab is looking for more survey participants. To learn more about this study or to participate in the survey, click here.

 

Learning from social isolation

by Heather Kosakowski |

“Livia Tomova, a postdoc in the Saxe Lab, recently completed a study about social isolation and its impact on the brain. Michelle Hung and I had a lot of exposure to her research in the lab. When “social distancing” measures hit MIT, we tried to process how the implementation of these policies would impact the landscape of our social lives.

We came up with some hypotheses and agreed that the coronavirus pandemic would fundamentally change life as we know it.

So we developed a survey to measure how the social behavior of MIT students, postdocs, and staff changes over the course of the pandemic. Our study is still in its very early stages, but it has been an incredibly fulfilling experience to be a part of Michelle’s development as a scientist.

Heather Kosakowski’s daughter in Woods Hole, Massachusetts. Photo: Heather Kosakowski

After the undergraduates left, graduate students were also strongly urged to leave graduate student housing. My daughter (age 11) and I live in a 28th-floor apartment and her school was canceled. One of my advisors, Nancy Kanwisher, had a vacant apartment in Woods Hole that she offered to let lab members stay in. As more and more resources for children were being closed or shut down, I decided to take her up on the offer. Wood’s Hole is my daughter’s absolute favorite place and I feel extremely lucky to have such a generous option. My daughter has been coping really well with all of these changes.

While my research is at an exciting stage, I miss being on campus with the students from my cohort and my lab mates and my weekly in-person meetings with my advisors. One way I’ve been coping with this reality is by listening to stories of other people’s experiences. We are all human and we are all in the midst of a pandemic but, we are all experiencing the pandemic in different ways. I find the diversity of our experience intriguing. I have been fortunate to have friends write stories about their experiences, so that I can post them on my blog. I only have a handful of stories right now but, it has been really fun for me to listen, and humbling for me to share each individual’s unique experience.”

Heather Kosakowski is a graduate student in the labs of Rebecca Saxe and Nancy Kanwisher where she studies the infant brain and the developmental origins of object recognition, language, and music. Heather is also a Marine Corps veteran and single mom who manages a blog that “ties together different aspects of my experience, past and present, with the hopes that it might make someone else out there feel less alone.”

#WeAreMcGovern

Three from MIT awarded 2020 Guggenheim Fellowships

by Julie Pryor |

MIT faculty members Sabine Iatridou, Jonathan Gruber, and Rebecca Saxe are among 175 scientists, artists, and scholars awarded 2020 fellowships from the John Simon Guggenheim Foundation. Appointed on the basis of prior achievement and exceptional promise, the 2020 Guggenheim Fellows were selected from almost 3,000 applicants.

“It’s exceptionally encouraging to be able to share such positive news at this terribly challenging time” says Edward Hirsch, president of the foundation. “A Guggenheim Fellowship has always offered practical assistance, helping fellows do their work, but for many of the new fellows, it may be a lifeline at a time of hardship, a survival tool as well as a creative one.”

Since 1925, the foundation has granted more the $375 million in fellowships to over 18,000 individuals, including Nobel laureates, Fields medalists, poets laureate, and winners of the Pulitzer Prize, among other internationally recognized honors. This year’s MIT recipients include a linguist, an economist, and a cognitive neuroscientist.

Rebecca Saxe is an associate investigator of the McGovern Institute and the John W. Jarve (1978) Professor in Brain and Cognitive Sciences. She studies human social cognition, using a combination of behavioral testing and brain imaging technologies. She is best known for her work on brain regions specialized for abstract concepts such as “theory of mind” tasks that involve understanding the mental states of other people. She also studies the development of the human brain during early infancy. She obtained her PhD from MIT and was a Harvard University junior fellow before joining the MIT faculty in 2006. Saxe was chosen in 2012 as a Young Global Leader by the World Economic Forum, and she received the 2014 Troland Award from the National Academy of Sciences. Her TED Talk, “How we read each other’s minds” has been viewed over 3 million times.

Jonathan Gruber is the Ford Professor of Economics at MIT, the director of the Health Care Program at the National Bureau of Economic Research, and the former president of the American Society of Health Economists. He has published more than 175 research articles, has edited six research volumes, and is the author of “Public Finance and Public Policy,” a leading undergraduate text; “Health Care Reform,” a graphic novel; and “Jump-Starting America: How Breakthrough Science Can Revive Economic Growth and the American Dream.” In 2006 he received the American Society of Health Economists Inaugural Medal for the best health economist in the nation aged 40 and under. He served as deputy sssistant secretary for economic policy at the U.S. Department of the Treasury. He was a key architect of Massachusetts’ ambitious health reform effort, and became an inaugural member of the Health Connector Board, the main implementing body for that effort. He served as a technical consultant to the Obama administration and worked with both the administration and Congress to help craft the Affordable Care Act. In 2011, he was named “One of the Top 25 Most Innovative and Practical Thinkers of Our Time” by Slate magazine.

Sabine Iatridou is professor of linguistics in MIT’s Department of Linguistics and Philosophy. Her work focuses on syntax and the syntax-semantics interface, as well as comparative linguistics. She is the author and coauthor of a series of innovative papers about tense and modality that opened up whole new domains of research for the field. Since those publications, she has made foundational contributions to many branches of linguistics that connect form with meaning. She is the recipient of the National Young Investigator Award (USA), of an honorary doctorate from the University of Crete in Greece, and of an award from the Royal Dutch Academy of Sciences. She was elected fellow of the Linguistic Society of America. She is co-founder and co-director of the CreteLing Summer School of Linguistics.

“As we grapple with the difficulties of the moment, it is also important to look to the future,” says Hirsch. “The artists, writers, scholars, and scientific researchers supported by the fellowship will help us understand and learn from what we are enduring individually and collectively, and it is an honor for the foundation to help them do their essential work.”