“Recent advances in surgical neuromodulation have enabled long-term continuous monitoring of brain activity in OCD patients during their everyday lives,” said Dr. Nicole Provenza, an assistant professor at Baylor College of Medicine and McNair Scholar. “We used this novel opportunity to identify key neural signatures that can act as predictors of clinical state in twelve individuals with treatment-resistant OCD who were receiving DBS therapy.”

DBS is emerging as an effective treatment for severe, treatment-resistant OCD

OCD is a common and debilitating mental health condition that affects 2-3% of the population worldwide. About two million people in the US suffer from OCD. In severe cases, patients spend an extraordinary amount of time performing repetitive, seemingly senseless compulsions and perseverating on intrusive thoughts. OCD has a huge toll on the well-being and quality of life of patients and their caregivers and can interfere with the ability to maintain employment and relationships. While psychotherapy and medications are effective in a majority of the affected individuals, approximately 20-40% of individuals with severe OCD are resistant to these conventional treatments.

Since the early 2000s, DBS therapy has been used to modulate neural activity in specific regions of the brain linked to OCD symptoms. Many patients who qualify for this therapy have not received sufficient benefit from conventional therapies. In this treatment-resistant population, roughly two-thirds of patients show significant improvement in OCD symptoms after DBS.

Much like how pacemaker devices regulate electrical activity in the heart, DBS devices regulate electrical activity in the brain. DBS devices carry electrical impulses from the generator, typically implanted in the upper chest, via a pair of thin leads (wires) to specific target regions in the brain. Precise tuning of the stimulation parameters allows the electrical pulses to restore a dysfunctional brain circuit to a healthy state.

DBS is an FDA-approved procedure commonly used to treat movement disorders such as essential tremors and Parkinson’s disease and is increasingly being used to treat severe OCD.

“We have seen remarkable progress in the field of DBS research, a technology that has been used for decades to treat movement disorders,” said Dr. John Ngai, Director of the Brain Research Through Advancing Innovative Neurotechnologies® Initiative (The BRAIN Initiative®) at the National Institutes of Health, which provided partial funding for this study. “The advance reported here represents just one on a growing list of success stories where the BRAIN Initiative has helped develop a new generation of DBS technologies, bringing treatments for conditions like OCD closer to the clinic.”

Need for a clinical biomarker to monitor OCD patient’s response to DBS

Defining the correct dose is oftentimes more difficult for psychiatric disorders like OCD than for movement disorders. “In patients with movement disorders, it is more obvious when stimulation delivery and tuning is correct because abnormal movements such as tremors or stiffness decrease right away,” said Dr. Sheth, professor and Vice Chair of Research in the Department of Neurosurgery at Baylor College of Medicine, director of the Gordon and Mary Cain Pediatric Neurology Research Foundation Laboratories, and investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital. “However, it is much more difficult to achieve this level of precise DBS programming for OCD and other psychiatric disorders because there is a long delay between stimulation initiation and symptom improvement. It is difficult to know what particular adjustment led to a particular change months later. Our goal in undertaking this study was therefore to find a reliable neural biomarker to guide us during DBS management, and to remotely monitor changes in our patients’ symptoms. This is particularly important because several of our patients travel long distances from around the country or world to get DBS treatment, which for OCD is currently offered only in very few specialized centers.”

Targeting the root of the OCD problem

To identify an optimal target for developing a biomarker, the team focused on one of the most characteristic behaviors in OCD — the tendency for pathological avoidance. Individuals with OCD often suffer from difficult-to-control avoidance of potential harm or distress. In trying to avoid such perceived threats in daily life, they are often plagued by intrusive internal thoughts and irrational fears (obsessions), which lead to rigid routines and repetitive behaviors (compulsions).

The team’s goal was to understand how low-frequency brain oscillations in the theta (4-8 Hz) to alpha (8-12 Hz) range, which have been found by a large body of scientific literature to play a prominent role in cognitive processes, were altered in individuals with severe, treatment-resistant OCD. To do so, they took advantage of a novel feature of modern DBS devices — the ability to not only deliver stimulation but also record brain activity.

Usually, studies that monitor brain activity patterns are designed to be brief episodes that are conducted as participants perform a specific cognitive task. However, this study is unique because the researchers were able to use the DBS system to continuously monitor brain activity patterns in the background of everyday activities. This feature of the study brought the research into the natural lives of the study participants rather than confining it to unnatural laboratory settings.

Recordings started upon implantation of the DBS system. Because stimulation is typically initiated days to weeks later, the team was able to measure neural activity patterns in the severely symptomatic state. Interestingly, they found that 9 Hz (theta-alpha border) ventral striatum neural activity demonstrated a prominent circadian rhythm that fluctuated over the 24-hour cycle.

“Before DBS, we saw an extremely predictable and periodic neural activity pattern in all participants,” said Dr. Goodman, professor and D. C. and Irene Ellwood Chair in Psychiatry in theMenninger Department of Psychiatry and Behavioral Sciences at Baylor College of Medicine. “However, after DBS activation, as individuals began responding and improving symptomatically, we saw a breakdown in this predictable pattern. This is a very interesting phenomenon and we have a theory to explain it. Individuals with OCD have a limited repertoire of responses to any given situation. They often perform the same rituals repeatedly and seldom vary their routines or engage in new activities, which may result in high predictability of activity in this brain region. However, after DBS activation, their behavioral repertoire is expanded; they might respond more flexibly to situations and not be just driven by a strong desire to avoid OCD triggers. This expanded repertoire may be a reflection of the more diverse brain activity pattern. Thus, we think this loss of a highly predictable neural activity indicates that the participants engaged in fewer repetitive and compulsive OCD behaviors.”

“In summary, we have identified a neurophysiological biomarker that can serve as a reliable indicator of improvements in mood and behaviors in OCD patients after DBS treatment. We anticipate these findings to transform how patients are monitored throughout DBS therapy,” added Dr. Sheth, who is also a McNair Scholar and Cullen Foundation Endowed Chair at Baylor College of Medicine.

“Incorporating this information into a clinician-facing dashboard, for example, could help guide therapy delivery, thus demystifying the process of DBS programming for OCD and making the therapy more accessible to a greater number of clinicians and patients. Moreover, we are excited by the potential possibility that such similar neural activity signatures may underlie other neuropsychiatric disorders and could serve as biomarkers to diagnose, predict, and monitor those conditions,” Dr. Provenza concluded.

Californians are familiar with landslides that occur around storms, when saturated soil and rock loses its grip and slips from its perch on the substrate. These types of landslides can be triggered by intense rainfall, and incoming storms can be a warning that neighborhoods need to evacuate.

Landslides that happen during the hot, dry summers, though, tend to take people by surprise. In July 2023, for example, a landslide seemed to come out of nowhere to devastate a neighborhood in Rolling Hills Estates, located on the northern side of the Palos Verdes Peninsula in Los Angeles County.

Now, landslide researchers at UCLA and NASA’s Jet Propulsion Laboratory, or JPL, have published a paper in Geophysical Research Letters that shows that the 2023 Rolling Hills Estates event was a slow-moving, progressive landslide that began the winter before, when unusually heavy rainfall infiltrated into the slope and reduced its strength. The researchers used satellite data to measure minute shifts in the surface of the affected area before, during and after the slide and concluded that this method could be used to detect future landslides before they become catastrophic.

“Movement on the Palos Verdes Peninsula’s Portuguese Bend Landslide has been recorded since the late 1950s,” said paper co-author Alexander Handwerger, a research scientist at UCLA’s Joint Institute for Regional Earth System Science & Engineering and JPL. “But there was no discernible movement in this region of the nearby Rolling Hills Estates before 2023. People began reporting movement, as indicated by cracks in houses, in April 2023, which matches our observations. There was initial slow movement that accelerated progressively, culminating in complete collapse several months later.”

The study, led by UCLA postdoctoral researcher Xiang Li, used satellite radar and optical data taken over Los Angeles every few weeks to measure ground motion over time. The satellite radar data for Rolling Hills Estates from 2016 to July 2023 revealed that after very slight movement during the 2019 rainy season, the ground remained stable until heavy winter rainfall, starting in December 2022, kickstarted movement in February. By June, the area had moved 0.04 meters, or about 1.6 inches, and on July 8 — a sunny, dry day preceded by 40 dry days — around 10 meters, or 33 feet, of horizontal motion occurred, destroying 12 homes.

The likely reason for the delay between initial movement in February and complete failure in July is that it took time for increased instability to develop. The researchers hypothesize that as water seeped through the ground, a sliding surface formed, causing the landslide body, including the ground surface, to slide progressively until the entire landslide moved rapidly all at once.

“Formation of the sliding surface will induce some movement, while the collapse will only occur when the sliding surface is fully developed,” Li said. “The progression can happen over hours, months or years.”

The researchers then attempted to determine if the Rolling Hills Estates landslide could have been predicted. By computing the displacement over time, they arrived at a predicted failure date on July 11, three days after the real landslide on July 8. They note that although their results are encouraging, predicting landslides using satellite remote sensing data needs further refinement, and landslides in areas without good historical satellite data might not be possible to predict in this way.

Li said that one of the challenges in forecasting landslides is the time period over which the progression takes place. Accurate forecasting requires continuous historical and ongoing satellite radar or in-situ measurements.

Handwerger is a core member of a project at JPL that is building an analysis-ready surface displacement database from satellite radar data for the entire United States, U.S. territories, Canada within 200 km of the U.S. border, and all mainland countries from the southern U.S. border up to and including Panama. The project, called Observational Products for End-Users from Remote Sensing Analysis, or OPERA, will contain analysis-ready data for near real-time monitoring and, possibly, landslide prediction.

“These motions can be quite subtle before they begin to move fast,” Li said. “Cracks in structures are what people tend to notice first. In fact, local residents in Rolling Hills Estates first reported cracks in their houses starting in April 2023. Signs of active movement require caution and monitoring because they could signal a progressive failure in the future.”

The study, in fruit flies and mice, also identified ways to block this process, which could have implications for treating or preventing the muscle wasting sometimes associated with inflammatory diseases, including bacterial infections, Alzheimer’s disease and long COVID.

The study is published July 12 in the journal Science Immunology.

“We are interested in understanding the very deep muscle fatigue that is associated with some common illnesses,” said senior author Aaron Johnson, PhD, an associate professor of developmental biology. “Our study suggests that when we get sick, messenger proteins from the brain travel through the bloodstream and reduce energy levels in skeletal muscle. This is more than a lack of motivation to move because we don’t feel well. These processes reduce energy levels in skeletal muscle, decreasing the capacity to move and function normally.”

To investigate the effects of brain inflammation on muscle function, the researchers modeled three different types of diseases — an E. coli bacterial infection, a SARS-CoV-2 viral infection and Alzheimer’s. When the brain is exposed to inflammatory proteins characteristic of these diseases, damaging chemicals called reactive oxygen species build up. The reactive oxygen species cause brain cells to produce an immune-related molecule called interleukin-6 (IL-6), which travels throughout the body via the bloodstream. The researchers found that IL-6 in mice — and the corresponding protein in fruit flies — reduced energy production in muscles’ mitochondria, the energy factories of cells.

“Flies and mice that had COVID-associated proteins in the brain showed reduced motor function — the flies didn’t climb as well as they should have, and the mice didn’t run as well or as much as control mice,” Johnson said. “We saw similar effects on muscle function when the brain was exposed to bacterial-associated proteins and the Alzheimer’s protein amyloid beta. We also see evidence that this effect can become chronic. Even if an infection is cleared quickly, the reduced muscle performance remains many days longer in our experiments.”

Johnson, along with collaborators at the University of Florida and first author Shuo Yang, PhD — who did this work as a postdoctoral researcher in Johnson’s lab — make the case that the same processes are likely relevant in people. The bacterial brain infection meningitis is known to increase IL-6 levels and can be associated with muscle issues in some patients, for instance. Among COVID-19 patients, inflammatory SARS-CoV-2 proteins have been found in the brain during autopsy, and many long COVID patients report extreme fatigue and muscle weakness even long after the initial infection has cleared. Patients with Alzheimer’s disease also show increased levels of IL-6 in the blood as well as muscle weakness.

The study pinpoints potential targets for preventing or treating muscle weakness related to brain inflammation. The researchers found that IL-6 activates what is called the JAK-STAT pathway in muscle, and this is what causes the reduced energy production of mitochondria. Several therapeutics already approved by the Food and Drug Administration for other diseases can block this pathway. JAK inhibitors as well as several monoclonal antibodies against IL-6 are approved to treat various types of arthritis and manage other inflammatory conditions.

“We’re not sure why the brain produces a protein signal that is so damaging to muscle function across so many different disease categories,” Johnson said. “If we want to speculate about possible reasons this process has stayed with us over the course of human evolution, despite the damage it does, it could be a way for the brain to reallocate resources to itself as it fights off disease. We need more research to better understand this process and its consequences throughout the body.

“In the meantime, we hope our study encourages more clinical research into this pathway and whether existing treatments that block various parts of it can help the many patients who experience this type of debilitating muscle fatigue,” he said.

The ozone layer, a crucial shield protecting life on Earth from harmful ultraviolet (UV) radiation, has been on a path to recovery thanks to the Montreal Protocol. This landmark international treaty, adopted in 1987, successfully led to phasing out the production of numerous substances responsible for ozone depletion. Over the past decades, the ozone layer has shown significant signs of healing, a testament to global cooperation and environmental policy.

However, the stability of this vital atmospheric layer is now facing a new and unexpected challenge. During the 2019/20 Australian wildfires, researchers observed a dramatic increase in stratospheric aerosols — tiny particles that can influence climate, health, and atmospheric chemistry.

Smoke-charged vortex transports aerosol up to 35 kilometers

Utilizing new satellite data and numerical modeling, the research team successfully demonstrated the impact of wildfires through a novel phenomenon: the smoke-charged vortex (SCV).

“The SCV is a powerful, smoke-laden whirlpool that transports wildfire smoke into the middle stratosphere, reaching altitudes of up to 35 kilometers,” explained Prof. Hang Su from the Institute of Atmospheric Physics at the Chinese Academy of Sciences, one of the corresponding authors of the study. “This process led to at least a doubling of the aerosol burden in the southern hemisphere’s middle stratosphere. Once reaching such high altitudes, these aerosols initiated a series of chemical reactions at their surface that impacted ozone concentrations.”

The international team discovered that these wildfire-induced aerosols facilitated heterogeneous chemical reactions in the stratosphere, which paradoxically led to both ozone depletion and ozone increase at different atmospheric layers.

While the lower stratosphere experienced significant ozone depletion, the new study shows that the increase of smoke aerosol particles in the middle stratosphere enhances the heterogeneous uptake and hydrolysis of N₂O₅, which leads to a decrease of reactive nitrogen gases, e.g., NOx, and an increase of ozone. In Southern Mid-Latitudes, the complex interplay managed to buffer approximately 40% (up to 70%) of the ozone depletion observed in the lower stratosphere in the following months of the mega-bushfire events.

So why does this matter?

“Our study uncovers an unexpected and crucial mechanism by which the absorbing aerosols in wildfire smoke, such as black carbon, can induce and sustain enormous smoke-charged vortices spanning thousands of kilometers, fundamentally changing the stratospheric circulation. The vortices can persist for months, carrying aerosols deeply into the stratosphere and affecting the ozone layer in distinct ways at different altitudes. This highlights the need for continued vigilance and research as climate change progresses,” said Prof. Yafang Cheng, another leading author from the Max Planck Institute for Chemistry.

“We’ve made a significant step forward in simulating the SCV as a new effective pathway for wildfires to modify stratospheric dynamics and chemistry, especially the ozone layer. I love this study because it once again demonstrates how closely different parts of the Earth system are connected. Smoke from a forest fire can significantly change the wind and circulation tens of kilometers above the ground, which allows the smoke to modify the ozone layer, influencing life on our planet,” said Dr. Chaoqun Ma, the first author of the study and postdoc researcher in Cheng’s team at the MPIC.

The ozone layer’s role in filtering UV radiation is crucial for protecting all life forms on Earth. The Montreal Protocol’s success in reducing ozone-depleting substances was a monumental achievement. Still, the new findings highlight that natural events, exacerbated by climate change, pose additional risks to this fragile atmospheric layer. With the increasing frequency and intensity of wildfires driven by global warming, the formation of SCVs and their impact on the stratosphere could become more common, posing a threat to the ozone layer.

The human brain is remarkably adept at adjusting what we hear based on contexts, like our current environment or priorities, but it’s still unknown how exactly the brain helps us detect, filter and react to sounds.

Now, biologists at the University of Maryland are a step closer to solving that mystery. Using an animal model, the researchers found that the orbitofrontal cortex (OFC), a brain region associated with decision-making but not typically linked to hearing, plays a central role in helping the auditory cortex (a primary hearing center of the brain) adapt to changing contexts or situations. The team’s findings were published in the journal Current Biology on July 11, 2024.

“Our hearing doesn’t just depend on the sounds around us. It also relies heavily on what we’re doing and what’s important to us at that moment,” explained UMD Biology Assistant Professor Melissa Caras, the paper’s senior author. “Understanding the neural mechanisms responsible for these adjustments can also lead to a better understanding of and potential treatments for neurodevelopmental disorders like autism, dyslexia or schizophrenia — conditions where sensory regulation goes awry.”

To closely examine the brain circuitry involved in the hearing process, the researchers turned to gerbils, small mammals whose basic hearing system is similar to that of humans. The animals were exposed to sound patterns in two different contexts. In one context, the animals listened to sounds passively without needing to do anything. In the other, the animals had to perform a specific action in response to the sounds they heard. By recording and manipulating the brain activity of the animals, the team discovered that the OFC helped the animals switch between passive and active listening.

“In short, the OFC sends signals to the auditory cortex when it’s time to pay closer attention to sounds,” Caras said. “It’s not certain whether the signals are sent directly or indirectly via an intermediary brain region, but we do know that activity in the OFC is essential to how the gerbils behaved in our experiments.”

When the OFC was silenced, the animals’ auditory cortex did not switch between passive and active listening, impairing their ability to pay attention to and react to a behaviorally relevant sound.

“In terms of a more human-oriented analogy, it would be as if I told you to suddenly pay attention to your refrigerator humming in the background,” Caras explained. “If your OFC was silenced and unable to send a signal to your auditory cortex, you might have difficulty doing so because the ability to rapidly alter your sound perception would be impaired.”

While this study was conducted in animals, Caras says the findings may have notable implications for human health and well-being. The ability to quickly shift attention to important sounds is essential for many day-to-day activities including communicating with others and navigating busy or dangerous environments.

“We’re just beginning to understand how the brain fine tunes hearing sensitivity in response to sudden shifts in behavioral contexts. We plan to explore exactly how the OFC communicates with the auditory cortex and see whether it’s possible to strengthen the connection and improve hearing ability,” Caras said. “This work is paving the way for researchers and health care professionals to develop better strategies for improving hearing in both healthy individuals and those with sensory impairments.”

This research was supported by the National Institutes of Health (Award Nos. R00DC016046 and R01DC020742).

Now, however, in a study published recently in the Journal of Clinical Immunology, researchers from Tokyo Medical and Dental University (TMDU) and Kagoshima University have identified a previously undocumented manifestation among patients with 18q del syndrome: late-onset combined immunodeficiency (LOCID), affecting both B and T cells. This novel finding underscores the critical importance of routinely assessing the functionality of both B and T cells in individuals with 18q del syndrome.

Elaborating further on this novel finding, Professor Kanegane says, “In this study, we came across two patients with chromosome 18q del syndrome presenting with LOCID, which, to the best of our knowledge, has not yet been reported in patients with the syndrome.”

Patient 1 was a 29-year-old man diagnosed with 18q del syndrome. Despite initially having few infections, he developed Pneumocystis pneumonia (PCP). Array-based comparative genomic hybridization (CGH) analysis showed a deletion in the 18q21.32-q22.3 chromosome region.

Patient 2 was a 48-year-old woman who had not been previously diagnosed with 18q del syndrome. However, she was diagnosed with granulomatous lymphadenitis, and a biopsy of her lymph nodes revealed a loss of 18q21.33-qter.

Both patients exhibited hypogammaglobulinemia, characterized by abnormally low levels of immunoglobulins (IgG, IgA, IgM, and IgE). Patient 1’s serum immunoglobulin levels were significantly below normal ranges. He reported IgG of 188 mg/dL (normal: 870-1,700 mg/dL), IgA of 105 mg/dL (normal: 110-410 mg/dL), IgM of 26 mg/dL (normal: 33-190 mg/dL), and IgE of <5 IU/mL (normal: 232 IU/mL). His CD4⁺ T cells had a decreased percentage of naïve T cells, accounting for only 3.58% of the total CD3⁺CD4⁺ cell population. Moreover, his T-cell receptor excision circles (TREC) levels and Ig κ-deleting recombination excision circle (KREC) levels were extremely low at 25.27 copies/105 cells (normal: > 565 copies/105 cells) and 93.36 copies/105 cells (normal: ≥ 456 copies/105 cells) respectively, indicating poor T-cell production.

Similar conditions were noted for patient 2, who reported IgG of 8 mg/dL, IgA of 9 mg/dL, IgM of 131 mg/dL, and IgE of 0.3 IU/mL. Her CD4⁺ T cells and naïve CD4⁺ T cells were depleted, with naïve T cells accounting for only 6% of the CD3⁺CD4⁺ cell population. Her TREC levels were 0 copies/10⁵ cells, and her KREC levels were 11.4 copies/10⁵ cells.

Importantly, CD4⁺ and CD8⁺ T cells failed to divide in response to phytohemagglutinin (PHA) stimulation, indicating severe functional impairment of T cells in both the patients.

Based on their immune profiles and clinical history, both of them were diagnosed with LOCID, a condition where both humoral (antibody-mediated) and cell-mediated immune responses were impaired, making them highly susceptible to infections.

This novel finding is significant, as Dr. Tomomasa, the co-authored of this study, states, “While cases involving deletion of the same region as those of the two patients presented in this study have been reported earlier, patients with 18q del syndrome developing LOCID have never been reported. We speculate that these patients simply have not yet developed LOCID or that they might not have been adequately assessed for it.”

On the basis of these results, the researchers recommend annual testing for both cellular and humoral immunity in patients with 18q del syndrome. This proactive approach can allow for the early detection of combined immune deficiencies, facilitating timely interventions and personalized treatment strategies. Ultimately, such regular monitoring can significantly improve clinical outcomes and enhance the quality of life for individuals diagnosed with 18q del syndrome.