A recent study has unveiled new insights into the neural mechanisms underlying treatment-resistant depression. By recording stereotactic electroencephalography signals (sEEG) from patients’ brains, the team identified specific abnormalities in how depressed individual process emotional information. This study, published in Nature Mental Health, provides a promising step towards understanding and potentially treating this challenging condition.
Depression is a common but serious mental health disorder characterized by persistent feelings of sadness, hopelessness, and a lack of interest or pleasure in daily activities. It affects millions of people worldwide and can significantly impair one’s ability to function at work, school, and in personal relationships.
While many individuals with depression respond well to standard treatments, such as medication and psychotherapy, a significant subset of patients do not experience sufficient relief from these approaches. This condition is known as treatment-resistant depression. It is defined as the failure to respond to at least two different antidepressant treatments administered at adequate doses and durations.
The new study conducted by the researchers at Baylor College of Medicine aimed to explore the neural basis of an emotion-processing bias observed in individuals with depression. This bias leads to a stronger response to negative information compared to positive information, which exacerbates depressive symptoms. Understanding the neural mechanisms behind this bias is crucial for developing targeted interventions that can better address the unique challenges of treatment-resistant depression.
“There has been a big question in the field about whether there was a physiological abnormality we could measure related to depression, as people had historically thought of it as a disorder of the ‘mind’ rather than one of the ‘brain’ and its cells. In this study, we were able to capture very sensitive data from awake, behaving human subjects that demonstrate a physiological basis for treatment-resistant depression,” said study authors Kelly Bijanki, an associate professor, and Xiaoxu Fan, a postdoctoral fellow.
For the study, sEEG electrodes were implanted in specific regions of the participants’ brains, particularly the amygdala and prefrontal cortex (PFC). These regions were chosen due to their known roles in emotion processing and regulation. The electrodes provided high spatial and temporal resolution recordings of brain activity, allowing the researchers to observe detailed neural responses to emotional stimuli.
The study included 12 epilepsy patients and 5 patients diagnosed with treatment-resistant depression. The epilepsy patients served as a control group since they were already undergoing stereotactic electroencephalography (sEEG) monitoring for seizure localization. The treatment-resistant depression patients had not responded to at least four different antidepressant treatments and were recruited as part of an early feasibility trial.
Participants were asked to rate the emotional intensity of human face photographs displaying various expressions, ranging from very sad to very happy. This task was designed to evoke and measure their neural responses to both positive and negative emotional stimuli. The emotional intensity ratings were recorded using a computer interface, ensuring precise synchronization with the brain activity data captured by the sEEG electrodes.
The researchers found that individuals with treatment-resistant depression exhibited a heightened and prolonged response in the amygdala when viewing sad faces compared to the control group. This increased activity began around 300 milliseconds after the sad faces were presented, indicating an overactive bottom-up processing system.
The treatment-resistant depression group also showed a reduced amygdala response to happy faces at a later stage (around 600 milliseconds). This finding suggests a diminished ability to process positive emotional stimuli, which may play a role in the persistent low mood characteristic of depression.
The researchers observed increased alpha-band power in the prefrontal cortex of the treatment-resistant depression patients during the late stage of processing happy faces. Alpha-band power is thought to reflect inhibitory processes in the brain.
Additionally, there was enhanced alpha-band synchrony between the prefrontal cortex and the amygdala, indicating stronger top-down regulation of the amygdala by the prefrontal cortex in these patients. This suggests that the prefrontal cortex may excessively inhibit the amygdala, contributing to the reduced emotional response to positive stimuli.
“sEEG can provide data with high temporal resolution and reliable anatomical precision of signal sources,” Bijanki and Fan told PsyPost. “With the help of sEEG, our results clearly revealed that different neural mechanisms are responsible for the biased negative and positive emotion processing in TRD patients.
The study also explored the effects of deep brain stimulation on neural responses in treatment-resistant depression patients. After deep brain stimulation was administered to the subcallosal cingulate and ventral capsule/ventral striatum regions, the neural responses to emotional stimuli in the patients showed significant changes.
The amygdala response to both sad and happy faces increased, and the alpha-band power in the prefrontal cortex decreased during happy-face processing. Furthermore, the alpha-band synchrony between the prefrontal cortex and the amygdala during happy-face processing was reduced, bringing the neural activity patterns closer to those observed in the control group.
“Treatment-resistant depression has a signature in the firing pattern of neurons in the brain, especially during an emotional task,” Bijanki and Fan explained. “We see the brain being perhaps overly sensitive to negative emotional information in depression patients, and we see evidence of increased top-down inhibition from a moderating brain region that may explain the abnormality. Further, we see after therapeutic brain stimulation, this pattern is normalized. We hope with further study this signal may help clarify the mechanism of depression and suggest new potential treatments.”
The small sample size limits the ability to generalize the findings. Additionally, using epilepsy patients as controls, who may have varying levels of depressive symptoms themselves, might affect the comparison. Future research should aim to include larger and more diverse samples to validate these findings.
The researchers also plan to explore how these neural markers can be used to evaluate the effectiveness of depression treatments. “We hope to use the biased emotional processing signature as a biomarker to evaluate the effects of depression treatments and as an indicator of the severity of depression symptoms in future patients,” the researchers said.
The study, “Brain mechanisms underlying the emotion processing bias in treatment-resistant depression,” was authored by Xiaoxu Fan, Madaline Mocchi, Bailey Pascuzzi, Jiayang Xiao, Brian A. Metzger, Raissa K. Mathura, Carl Hacker, Joshua A. Adkinson, Eleonora Bartoli, Salma Elhassa, Andrew J. Watrous, Yue Zhang, Anusha Allawala, Victoria Pirtle, Sanjay J. Mathew, Wayne Goodman, Nader Pouratian, and Kelly R. Bijanki.
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DATE:
June 16, 2024 at 06:00AM
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TITLE:
New research highlights the alarming impact of sleep deprivation on cognitive function
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URL: https://www.psypost.org/new-research-highlights-the-alarming-impact-of-sleep-deprivation-on-cognitive-function/
<p>A recent study published in <a href="https://doi.org/10.1007/s00221-024-06826-7"><em>Experimental Brain Research</em></a> has shed new light on how total sleep deprivation impacts the brain’s ability to process and integrate multiple stimuli presented in quick succession. The researchers found that a complete day without sleep significantly impairs both attentional and temporal integration mechanisms. In other words, going without sleep for a whole day seriously hinders our ability to pay attention and process information quickly, which is crucial for reacting correctly to fast changes around us.</p>
<p>Humans have a limited ability to process several events when they occur simultaneously or in quick succession. This limitation is evident in a phenomenon known as the attentional blink. The attentional blink is the difficulty people have in identifying the second of two stimuli presented closely together in time. The study aimed to explore how total sleep deprivation affects this phenomenon, given the known effects of sleep loss on various aspects of attention and perception.</p>
<p>“Initially, as a student, I was interested in studying the brain. After joining the <a href="https://cronobiologia-monterrey.blogspot.com/" target="_blank" rel="noopener">Laboratory of Psychophysiology</a>, I had the opportunity to delve into other topics that were very interesting to me, such as biological rhythms and sleep, or the limits in human neuropsychological capacities like attention and memory,” said study author <a href="https://scholar.google.com.mx/citations?user=bF1xaVEAAAAJ&hl=es" target="_blank" rel="noopener">Carlos Gallegos</a> of the Autonomous University of Nuevo León.</p>
<p>To understand how total sleep deprivation affects attention, the researchers designed an experiment involving 22 undergraduate students. These students, aged around 17 years, had no health or sleep disorders. The study ensured they followed a regular sleep schedule before participating. They stayed at a laboratory for six consecutive days, undergoing different conditions to test their attention under various levels of sleep.</p>
<p>The experiment was divided into three main phases: For two nights, participants slept at least 8 hours to establish their normal level of attention. On the fourth day, participants stayed awake for 24 hours straight. Participants were allowed to sleep freely for two nights to see if their attention levels returned to normal.</p>
<p>The researchers used a task called the Rapid Serial Visual Presentation (RSVP) to measure attention. In this task, participants had to identify two target numbers mixed among a series of distractor letters shown rapidly on a computer screen. The accuracy of identifying these numbers at different time intervals helped measure the attentional blink.</p>
<p>After 24 hours without sleep, participants’ ability to accurately identify the target numbers dropped significantly. This decline in performance was restored after the participants had two nights of unrestricted sleep, indicating that sleep is crucial for maintaining attention.</p>
<p>Sleep deprivation extended the time during which participants struggled to identify the second target number. Normally, the attentional blink occurs at intervals of 200-500 milliseconds, but sleep-deprived participants had difficulty even at 600 milliseconds. This extension suggests a significant impairment in the brain’s ability to process successive stimuli quickly.</p>
<p>“The main takeaway is that skipping a night of sleep can increase the risk of making errors,” Gallegos told PsyPost. “While some errors are harmless (such as misreading a word while studying), others can be fatal (like pressing the accelerator instead of the brake while driving). It’s important to emphasize that when we push capacities like attention and memory to their limits (as it occurs in the Attentional Blink), there’s always a chance of error, even during the day or without sleep deprivation.”</p>
<p>The magnitude of the attentional blink, which measures how much the accuracy of identifying the second target drops during the attentional blink interval, was reduced during sleep deprivation. This reduction was primarily due to an overall drop in accuracy for both targets, particularly the second one. The attentional blink magnitude returned to normal levels after the recovery sleep, highlighting the temporary but severe impact of sleep deprivation.</p>
<p>Under normal conditions, if the second target appears very shortly (within 100 milliseconds) after the first, both are usually identified correctly — a phenomenon known as lag-1 sparing. However, this effect disappeared during sleep deprivation, indicating impaired temporal integration mechanisms. This means the brain’s ability to process and integrate information presented in quick succession was compromised.</p>
<p>Participants also made more errors by identifying the target numbers in the wrong order during sleep deprivation, especially within the intervals up to 400 milliseconds. This increase in order reversals suggests that sleep deprivation extends the period during which the brain integrates multiple stimuli, leading to confusion.</p>
<p>“In our task to measure the Attentional Blink, stimuli were presented rapidly, individually, and successively, and participants had to identify two numbers (targets) among letters (distractors),” Gallegos explained. “When stimuli appear in direct succession (without distractors in between), people often identify the first stimulus as the second and vice versa. This inversion in reporting the order of stimuli is even greater with sleep deprivation. This result suggests that there are some perceptual alterations that could lead to errors in selecting (attending) the correct stimulus.”</p>
<p>These findings have significant implications for individuals who frequently experience sleep deprivation, such as medical professionals, pilots, and others in high-stakes jobs. The study suggests that even after 24 hours of wakefulness, people’s ability to process rapid changes in their environment is severely compromised. This impairment increases the risk of errors in tasks that require quick responses.</p>
<p>“Pushing functions like attention and memory to their limits can be dangerous during the day, even with adequate sleep,” Gallegos noted. “The risk increases during the night and with sleep deprivation. Nowadays, it’s very common, especially with the use of technology, for people to multitask. This is a very common way of pushing our processes to the limit.”</p>
<p>“During the research on the limits of attention, we have learned that there are limits in other fundamental processes that operate simultaneously, such as perception and memory. I would like to further study the limits in these capacities and gain a better understanding of how these functions relate to each other.”</p>
<p>“Hopefully in the future, society will place more value on these two topics that are quite common,” Gallegos added. “On one hand, sleep, which is a necessity that we often neglect to meet the demands of daily life. On the other hand, the limit of cognitive capacities, which we also frequently push when engaging in various activities simultaneously.”</p>
<p>The study, “<a href="https://link.springer.com/article/10.1007/s00221-024-06826-7">Total sleep deprivation effects on the attentional blink</a>,” was authored by Carlos Gallegos, Candelaria Ramírez, Aída García, Jorge Borrani, and Pablo Valdez.</p>
DATE:
May 16, 2024 at 03:32AM
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<p>A new study published in the <a href="https://www.sciencedirect.com/science/article/abs/pii/S0165032724005263"><em>Journal of Affective Disorders</em></a> has found that individuals who engage in gardening are less likely to suffer from multiple sleep complaints compared to those who do not exercise. The research highlights gardening as a beneficial activity potentially leading to better sleep quality, including fewer instances of insomnia, daytime sleepiness, and sleep apnea.</p>
<p>The interest in sleep health has grown significantly due to its crucial role in overall wellbeing. Previous research has connected poor sleep with an array of serious health issues, such as heart diseases, neurodegenerative disorders, and even an increased risk of death. Recognizing the need for effective strategies to combat sleep-related problems, researchers turned their attention to gardening—previously noted for its low injury risk and beneficial impacts on health—as a potential aid to improve sleep patterns.</p>
<p>“According to the <a href="https://health.gov/healthypeople/tools-action/browse-evidence-based-resources/physical-activity-guidelines-americans-2nd-edition" target="_blank" rel="noopener">Physical Activity Guideline for Americans</a> (2nd edition), gardening is a muscle-strengthening and multicomponent physical activity with one of the lowest injury risks, which is appropriate and recommended for older adults,” said study author <a href="https://sph.fudan.edu.cn/employee/158">Xiang Gao</a>, a dean and distinguished professor at Fudan University.</p>
<p>“The benefits of gardening for physical and psychological health was well-established. However, the gardening-sleep association among the community population remained unrevealed. Therefore, this study aimed to explore whether gardening was associated with sleep complaints.”</p>
<p>For their study, the researchers analyzed data from the 2017 Behavioral Risk Factor Surveillance System (BRFSS), a comprehensive health-related telephone survey that gathers data annually across the United States. The survey included a wide range of questions on health behaviors, chronic diseases, and preventive measures, with specific modules on physical activity and sleep complaints examined for this study. The initial sample consisted of 85,148 adults from ten different states. However, due to incomplete information on physical activity and sleep outcomes, the final sample size was narrowed down to 62,098 adults.</p>
<p>Participants were categorized based on their engagement in physical activities, specifically distinguishing between non-exercisers, gardeners, and other exercisers. Gardeners were identified based on their responses to the physical activity module, where gardening needed to be listed as one of the two most time-consuming exercises they engaged in. This group was further divided into tertiles based on the duration of gardening per week, which allowed the researchers to analyze the effects of varying intensities of gardening on sleep health.</p>
<p>The analysis revealed that both gardeners and other exercisers showed a lower likelihood of experiencing multiple sleep complaints compared to non-exercisers. The odds ratios adjusted for potential confounders (like demographics, lifestyle, and chronic health conditions) highlighted that gardeners had a 42% lower likelihood of having multiple sleep complaints compared to non-exercisers. Other exercisers had a slightly less pronounced benefit, showing a 33% lower likelihood compared to non-exercisers.</p>
<p>Furthermore, the study uncovered a dose-response relationship between the amount of time spent gardening and sleep complaints. As the duration of gardening per week increased, the likelihood of having multiple sleep complaints progressively decreased. This trend remained significant even when controlling for various confounding factors.</p>
<p>On the level of individual sleep complaints, gardeners reported lower incidences of short sleep duration, probable insomnia, and daytime sleepiness compared to non-exercisers. The effects on sleep apnea were less clear, with no significant improvements observed for gardeners or other exercisers over non-exercisers. This pattern suggests that while gardening can positively impact several aspects of sleep, its effects may vary depending on the specific sleep issue considered.</p>
<p>These findings suggest that gardening has potential health benefits that extend into improving sleep quality and reducing the prevalence of common sleep disorders.</p>
<p>“As a valuable non-pharmaceutical intervention and an aerobic physical activity, gardening could be more strongly recommended for adults to minimize their likelihood of sleep complaints,” Gao told PsyPost. “The findings encourage the adults to participate in gardening activity, such as watering the field and growing vegetables.”</p>
<p>While the study provides compelling evidence supporting the benefits of gardening on sleep health, there are limitations due to its cross-sectional nature—mainly, the inability to definitively establish causality. The reliance on self-reported data could also introduce bias.</p>
<p>The study’s authors recommend further prospective studies to confirm these findings and to explore the mechanisms through which gardening could influence sleep health. Understanding these pathways can help in developing targeted interventions to harness the therapeutic benefits of gardening.</p>
<p>“We are committed to exploring the associations between gardening and health,” Gao said, adding that his research team has also found a positive link <a href="https://doi.org/10.1016%2Fj.jand.2022.10.018" target="_blank" rel="noopener">between gardening and cardiovascular health</a>. “Additionally, we will continue to examine the associations between gardening and odds of subjective cognitive decline, and explore the potential pathways underlying the gardening-cognition relationship.”</p>
<p>The study, “<a href="https://www.sciencedirect.com/science/article/abs/pii/S0165032724005263" target="_blank" rel="noopener">Association between gardening and multiple sleep complaints: A nationwide study of 62,098 adults</a>,” was authored by Kaiyue Wang, Yaqi Li, Muzi Na, Chen Wang, Djibril M. Ba, Liang Sun, and Xiang Gao.</p>