A Potential Direction for TMR

The beauty of Dr. Paller’s work lies in the support for applying his findings to other subjects and disciplines. If targeted memory reactivation (TMR) improves learning and memory cognition via auditory cues during sleep, would it be possible to use this kind of technique to improve psychiatric treatment for amnesiac patients? Although Dr. Paller mentioned ethical concerns regarding the possibility of "memory control," applying his approach to music-memory therapies might present an advantage.

During Dr. Paller's presentation, he introduced other examples that were not strictly declarative memory. Other projects demonstrate that TMR during sleep enhances performance in musical ability and learning to dissociate between social/gender biases. Increasing the complexity of the learning objectives would prove the effectiveness of TMR. However, what if this also works in a "backward" fashion?

Music-therapy has been rising in popularity at amnesiac patient care centers for the past few years. Patients can find ways to make associations and connections through auditory mediums, like music. "It [music] engages the totality of the brain — centers that process ... sound, memory, attention, language, sight, touch and more. It sparks neural activity within each of these centers and sets them in motion together in a way few other experiences can", stated Dr. Nina Kraus (Northwestern University) during an interview with the Chicago Tribune.

Relating this phenomenon to Dr. Paller's work, TMR during sleep may include the songs that connect with amnesiac patients as auditory stimuli and help them associate new (learned) memories with their preconvictions of the music. Even if this is an initial idea, the power of TMR should not be underestimated.

The news articles and corresponding videos regarding Music-Therapy are linked below.

A. Baird, S. SamsonMemory for music in Alzheimer's disease: Unforgettable?

Neuropsychology Review, 19 (1) (2009), pp. 85-101

Recognition of familiar and unfamiliar melodies in normal aging and Alzheimer's disease

Memory and Cognition, 23 (5) (1995), pp. 531-546

http://www.chicagotribune.com/news/ct-bert-rose-music-alzheimers-met-20150306-story.html

https://musicandmemory.org/

Circadian Rhythms and Sleep Affect College Students Learning

Recently, two significant people in the field of neuroscience recently gave a presentation of their current studies. The first speaker was Dr. Cavanaugh, in his discussion, he demonstrated what is currently known about the relationships between sleep and circadian rhythms. He demonstrated how there are distinct differences between the two topics. He first described sleep, which is regulated by our circadian clock which then causes a person to lose the responsiveness to their environment and external stimuli. He also stated that sleep is differentiated from a coma by its quick reversibility, which allows us to wake up at will. In contrast, circadian rhythms are known for their influence on the body. One of their main impact is to provide, “timekeeping in both clock neurons and peripheral tissues”. This allows a person to develop better sleeping patterns and regulates the secretion of melatonin at constant times throughout the week.

Our next speaker, Dr. Paller also focused on sleep. He studies how sleep impacts learning and declarative memory. We currently know that sleep naturally assists in the learning process. In his study, he discusses the effects on how sleep significantly improves learning in melodies and muscle movements. One of his studies demonstrated that listening to a melody while sleeping increased a person’s recollection of a particular memory when asked to perform a specific task. This is significant because it demonstrates that memory and learning can actually be impacted while sleeping.

Interestingly, when one juxtaposes the studies of Dr. Cavanaugh and Dr. Paller, the results can be directed into a discussion of an average college students sleep schedule. This topic has become a common discussion with the increase in people attending college in recent times. Considering the sleep deprivation that is a common challenge for college students, sleep, circadian rhythms and learning are critical to understand to better help and inform college students. Students are constantly disrupting their circadian rhythm to stay up to study for class, while this action may actually be damaging their performance in the long run.

CNN reported a recent study in which 61 students from Harvard College performed a research experiment in which they were separated in two different groups, regular sleepers or irregular sleepers. These groups were based on the time in which each student went to sleep. Experimenters were studying how sleep affects GPA. The researchers developed a scoring index that measures from 0-100, students would get ranked according to sleeping patterns. Irregular sleepers would be near 0 and regular sleepers would be near 100. What they found was that GPA’s would increase by .1 for every 10 points in their scoring index. According to Dr. Cavanaugh, the circadian rhythm is known for establishing adequate timekeeping for neurons. However, when there is irregular sleeping, there is a negative effect on the circadian rhythm that is responsible for regulating sleep. In addition to that, we know from Dr. Paller’s study that sleeping is critical for learning and memory. If there is an irregular sleeping pattern that is affecting the circadian rhythm, that will lead to less sleep. Due to the lack of sleep, this will begin to damage the memory and learning process that occurs during sleep. According to Dr. Czesler, he states that because the circadian rhythm is so drastically out of tune, it causes a biological time change in the body, meaning that, “an 8 a.m. class is a 5 a.m. class in biological time.” This means that the body is constantly out of rhythm, especially when it comes to the secretion of melatonin, an important hormone for sleeping. This all comes back to the resulting effect of an irregular circadian rhythm, which eventually leads to a lack of sleep. Dr. Paller demonstrated in his study that sleep has a connection with increased learning, and if a student lacks sleep, then it makes logical sense that it results in a lower GPA.

Overall, sleep is still widely unknown, however, we continue to increase our knowledge about it constantly. Thanks to research from Dr. Paller and Dr. Cavanaugh, we were able to better understand how the circadian rhythm functions in regulating sleep and how sleep is capable of helping the learning process.

The Secret to College Success?

I spend a majority of my time thinking about sleep, especially how I wish I had gotten more the night before. I am probably not the only college student feeling this way. In reality, sleep is not just a luxury college students don’t have time for, rather it is a vital and beneficial pursuit. In fact, I was recently convinced that my social and academic college performance depends on my making time for sufficient sleep every day. This is very exciting!  Neuroscience can provide the perfect excuse to get more sleep.

Dr. Cavanaugh‘s talk presenting his research into circadian rhythms of fruit flies and the application to humans peaked my interest. The main problem with sleep deprivation is that sleep debt is incurred. While some sleep debt can be “repaid” with extra hours of sleep the next night, the effects of losing sleep cannot all be erased. Most disturbingly, sleepless nights are also associated with neurodegeneration in areas of the brain that are not known to regenerate neural cells. Yikes!

 As usual when it comes to health, the best tactic for getting my attention and motivating me to do better is scaring me with the shocking outcome of my unhealthy behaviors. Therefore, hearing that repeated sleepless nights can result in irreversible neurodegeneration got my attention. Further pursuit of the subject led me to the fascinating topic of the effects of sleep deficits. In the article “The Hidden Costs of Sleep Deficits”, multiple studies on the subject of sleep deprivation showed alarming results.

According to Dr. Walker of UC Berkeley, sleep enhances the performance of every organ in the body. Furthermore, there is a strong correlation between sleep and emotion: the ability to regulate your own emotions as well as recognize others’ emotions is lessened by sleep debt. Therefore social situations become more precarious to navigate by the sleep-deprived brain of a college student. Loss of sleep is harmful even to the point of harming relationships with loved ones. The lab of Gordon and Chen at UC San Francisco found that conflict resolution was impaired when one partner was low on sleep. If just one partner was low on sleep, couples were less likely to work out arguments than well-rested couples.

Work is also negatively affected by lack of sleep: sleep-deprived people not only make more mistakes but are unaware of making them. Shockingly, this includes increasing unethical behavior. Business students participating in a study by Michael S. Christian of North Carolina University at Chapel Hill and Aleksander P.J. Ellis of University of Arizona were given a short test to take. The participants were told they received a dollar for every question answered correctly. The participants were allowed to grade their own tests and to take a dollar from the money envelope for each correct answer. The sleep-deprived business students were more likely to take more money than they had actually earned compared with the well-rested students. Finally, even the 40 minutes less of sleep around daylight savings time results in increased auto and workplace injuries!

Since sleep deficit can harm relationships, behavior, decision-making and even personal safety, sleep is vital for all college students seeking success in social as well as academic situations. The article shows that sleep is important for all aspects of health, so maybe we should make time for it just like healthy meals and time at the gym. So, I issue a challenge to myself and to all college students to proactively prioritize sleep, carving out time for it every day and intentionally sticking to bedtime.

Finally, an interesting question for further research on all the sorely under-slept college students is how much sleep deprivation does it take for irreversible neurodegeneration to result?

Reference: 

Report, O. S. (2017, November 30). The Hidden Costs of Sleep Deficits. https://www.psychologicalscience.org/observer/the-hidden-costs-of-sleep-deficits

A New Form of A.I.

People fear that power of artificial intelligence, but the more that we bridge the gap between robotics and mind power, that suspicion starts to become more of a reality. The New York Times published an article titled, "Prosthetic Limbs, controlled by thought" which, as the title speaks for itself, follows the journey of Les Baugh, a 50 year old man without either of his arms. Like many amputees, his injury was provoked by dedicating his service to fighting in the army. Biomedical engineers from John Hopkins University are one of the forefront runners examining this new age of revolutionary prosthetics. Dr. Kuiken also works with John Hopkins to expand on prosthetics' surgical procedure of Targeted Muscle Reinnervation. The New York times briefly covered the extent of the procedure for the sake of reaching a wider target audience. Though, this idea allows doctors and engineers to pinpoint areas of remaining free nerve endings from the amputee's muscles. From there, engineers utilize real time myoelectric control to connect those nerves onto the newly engineered artificial arm. In one of Mr. Baugh's' reoccurring meetings with his doctors, they examine any ounce of sensation by touching around the patient's injured site. (This phenomena is also known as ghost limb) Next, the doctors can map out each sensation that would have be formally moved by the ghost limb. Mr. Baugh's surgery was a success and he can execute any action with ease and he can't be any more gratified and humbled. I love how his doctor put it simply: "the limb should be apart of them, not them becoming apart of the machine." Future research, which luckily is funded by over 120 million dollars, is looking to integrate sensory caps onto artificial limbs. In addition, the main trajectory of this process is to make the prosthetic more much commercialized so that patients don't have to deal with (at starting price) the $500,000 burden. To me, Artificial Intelligence is modeled after the human anatomy and physiology. So by perfecting mind control with prosthetics, I believe that a new of robotics are underway regardless of whether or not that may scare you. 

References: 

https://www.nytimes.com/2015/05/21/technology/a-bionic-approach-to-prosthetics-controlled-by-thought.html

Kuiken, T. A., Li, G., Lock, B. A., Lipschutz, R. D., Miller, L. A., Stubblefield, K. A., & Englehart, K. (2009). Targeted Muscle Reinnervation for Real-Time Myoelectric Control of Multifunction Artificial Arms. JAMA : The Journal of the American Medical Association, 301(6), 619–628. http://doi.org/10.1001/jama.2009.116

The Real-life Applications of Targeted Memory Reactivation during sleep

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808124/bin/fnhum-12-00028-g001.jpg

Sleep has long been known by scientists and the public to play an important role in memory and have certain effects on our tendencies towards certain behaviors during consciousness, as well as our brains’ abilities to fortify fragile short-term memories into long-term memories. Though their effectiveness has not been scientifically proven, many companies have advertised their own products that play subliminal messages during sleep to help consumers quit addictive behaviors such as smoking. Targeted Memory Reactivation (TMR), the basis of Ken A. Paller and Renee E. Shimizu et. al’s studies, has been proven to be more crucial to sleep learning, as it reiterates information learned during consciousness rather than introducing new information during sleep, as addiction-reduction recording companies do.  

Paller’s article, “Sleeping in a Brave New World: Opportunities for Improving Learning and Clinical Outcomes Through Targeted Memory Reactivation,” explains the positive effects of sleep on memory consolidation. By playing auditory cues while participants performed memory formation tasks and then playing the same cues while the participants slept, memory retention and learning curves were shown to be dramatically increased in comparison to control participants who had not received TMR. Paller references a study by Staresina et. al. wherein slow oscillations (SOs), thalamocortical sleep spindles, and hippocampal sharp-wave ripples were crucially involved in memory consolidation during sleep.  

A study conducted by Shimizu et. al in Frontiers in Human Neuroscience also emphasizes the role of SOs, sleep spindles, and sharp-wave ripples occurring during Non-REM sleep that help consolidate declarative memories formed during consciousness. While Paller’s study focuses on the role of TMR to help consolidate memories associated with skill and habit learning or bias reduction, Shimizu’s study focuses on spatial and directional navigation improvement using the same mechanism. In this way, Paller and Shimizu et. al have opened a discussion about the diverse applications of TMR on learning and memory.

The participants of Shimizu et al.’s study were made to navigate the streets of a virtual city (using Oculus VR headsets) while auditory cues (such as a the sound of a pipe dropping while participants crossed the street in an industrial district) were played in the background. The same auditory cues were then played again while participants slept. The researchers developed a closed-loop TMR mechanism (CL-TMR) which only played the cues at times when participants’ brains produced electrical signals (through EEG recordings) that showed DUPT (down-state to up-state transitions), indicating the occurrence of slow-wave sleep spindles. The results of the study showed that these specifically timed auditory cues were more effective in improving memory consolidation, as participants who underwent CL-TMR later found destinations in the virtual city more quickly than those who did not receive CL-TMR. These findings were eye-opening, as I have personally struggled with directional cues and navigational memory, and would find Shimizu et. al’s application of CL-TMR to be very useful in my own life.  

As we can see, both researchers singled out the same sleep patterns during NREM (sharp-wave ripples, SO’s, and spindles), but Shimizu et. al went a step further through his development of the CL-TMR software to single out DUPTs (down-state to up-state transitions) during a participant’s sleep cycle. The real-life applications of this technology have been shown to be very diverse, as Paller introduced the cognitive and behavior-reinforcement functions of TMR, and Shimizu et. al found the navigational memory improvement functions. Therefore, CL-TMR technology has the ability to one day be commonly used and be effective for students or directionally-challenged individuals like myself.

Shimizu's et. al's article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808124/

A Glance at Today’s World through a Scientific Lens

There was a time when a popular belief was that our sensory systems are inhibited during sleep. This consensus discouraged researchers to look further into what may occur in our brains during sleep: the idea of brain activation during sleep was made inconceivable. However, an exception to this belief transpired due to the reported information on the olfactory system. It was identified as the only sensory system that displayed activity during sleep. Research on the olfactory system was conducted by Rasch Buchel, who studied how odors, when presented during sleep, influence our ability to formulate memories. In his study, he associated specific odors with new memories and later presented the same odors during sleep. Then a test was administered in order to document how well the memories could be recalled. Analysis of this experiment indicated that exposure to an odor during slow wave sleep, versus no exposure, promoted the consolidation of memories. Nevertheless, instead of allowing this research to inspire implications of other sensory systems, it was constrained to the view that the majority strongly believed in. Therefore, it was solely identified as an exception, implying that other proposed hypotheses on other sensory systems to be incompetent.

Even though the majority sustained power to their claim a minority of researched desired to disrupt that hold.  Fortunately, researchers that belonged to the minority at the time continued seeking other possibilities. A recent researcher, by the name of Umberto Olcese, who published in The Journal of Neuroscience in 2017, is one of many that addressed the common belief that the brain was disconnected throughout non-REM sleep accompanied by inhibited communication between the brain regions. His discovery among others, was able to disprove the long lived belief by providing evidence that not all communication associated within the cerebral cortex are lost during non-REM sleep. Olcese emphasized that neurons located in specific regions of the brain as well as various subpopulations in cerebral areas indeed maintain their associations in each area. This conclusion was determined by studying how the neural connections of the neocortex and hippocampus were regulated by the brain in rat models. This astounding evidence of activity throughout the various parts of the brain immediately surpassed the initial prominent claim.

Another researcher, Ken A. Paller, a professor and  neuroscientist at Northwestern University, acquired interest in how memory is affected by sleep. His research is inspired by the work of Rasch Buchel. Instead of using odor to determine the resulting associations among sleep and the consolidation of memory using the olfactory system as Buchel did, Paller decided to test the auditory system. He did this by first playing specific sounds, like a cat meowing, while presenting  a new memories. Later on, while the participant was asleep he played those same sounds loud enough to make sure the participant stayed asleep. Then he tested how much they recalled from the new set memories given in the beginning of the experiment. The results revealed a significant distinction between the participants that were cued the sounds (the experimental group) and those who were not (control group). The cued participants with the sounds showed a decrease in forgetting the new memories. On the other hand, the control group forgot almost twice as much of the memories when compared to the experimental group. This supports that there indeed are connections occurring between the brain and auditory system during sleep, which essentially revealed to aid consolidation of memories, once again disproving what was strongly believed before.

This scientific outlook allows us to see how influential our opinion can be, especially when it complies with the majority belief versus the minority. The major belief that the brain is simply “shut down” during sleep was enhanced and maintained by its believers. They were so focused on generating and maintaining the power of their claim that they began to blind themselves when it came to questioning if their claim was legitimate or not. If this claim continued to prevail and discredit any information that said otherwise, today the development and discoveries of Umberto Olcese, Rasch Buchel and Ken A. Paller would be irrelevant and we would still be in the dark about the possibility of brain activity during sleep. If the minority group of researchers decided not to take a leap in the opposite direction from society, then we would solely know the information the majority feeds us. Although this is a scientific example about claims and hypotheses established by scientists, it is not that far fetched to think we encounter this in our world continuously. In relation, it is evident that the president of the United States won by the majority of votes throughout the country. Just as the initial claim about our brains not experiencing activity, the President’s claims gained power due to his believers, who generated and sustained its power. This is why, a Journalist by the name, Nick Cohen, titled his piece, Trump’s lies are not the problem. It’s the millions who swallow them who really matter. If the majority of people continue to comply with his clams, what does that mean for our further development and discovery?

Works Cited
SINC. "Brain is still 'connected' during non-REM sleep." ScienceDaily. ScienceDaily, 1 December 2017.        .

Cohen, Nick. “Trump's Lies Are Not the Problem. It's the Millions Who Swallow Them Who Really Matter | Nick Cohen.” The Guardian, Guardian News and Media, 4 Feb. 2017, www.theguardian.com/commentisfree/2017/feb/05/donald-trump-lies-belief-totalitarianism.

Susanne Diekelmann, Jan Born, Björn Rasch
Front Behav Neurosci. 2016; 10: 74. Published online 2016 Apr 12. doi: 10.3389/fnbeh.2016.00074

fMRI: Answering the Questions that we don’t know, and correcting the answers that we thought we knew

           Medical technology is constantly advancing which leaves the door open for us to uncover the endless amount of medical discoveries that are out there. Research involving brain mapping and neural activities through the use of fMRI is helping researchers get a more detailed depiction of what is happening inside our brains which in turn will lead to better patient care.

Dr. Elizabeth Wakefield recently spoke at our seminar class about research that she has been working on involving the use of fMRIs and testing whether children essentially learn better by simply observing an action being done or whether they learn better by observing the action and then doing the action themselves. Results showed that there is higher motor cortex activation when the actions are self-generated showing evidence that learning through self-generated actions could prove to be a more beneficial way of learning in young developing brains in children. It’s information like this that helps lead to certain reforms that will benefit society. In the case of Dr. Wakefield’s research, this evidence may lead to improved methods of teaching in schools for children that may possibly result in an increased rate of educational advancement among children.

Like I mentioned earlier, advancement in medical technology is helping us make new discoveries, and some of these discoveries are things that we once thought were correct in the past but are no longer the case given the new types of evidence presented. This is currently the case in how doctors once believed infants perceived pain. The notion in the past was that infants perceived pain differently than older children and adults meaning that they received different clinical care for pain. Most infants that underwent surgical procedures or infants that were in the intensive care unit received no proper pain management. Instead, the methods of pain management consisted of cuddling and feeding which in itself only relieved the infant of distress but did nothing in terms of any physiological relief, meaning the pain was still present.

Dr. Sezgi Goksan and his partners have conducted research that has helped discover that infants and adults perceive pain in an almost identical fashion. The experiment they did consisted of acute noxious stimulation to both the infant and adults at a range from 32mN to 512mN. The participants underwent an fMRI during the acute noxious stimulation which recorded the changes in blood oxygen level dependent activity in the brain. The results showed that activity was recorded in 18 out of 20 active adult brain regions. The two regions that were inactive in the infant brain were the amygdala and orbitofrontal cortex. What this means is that there are some differences in perception of pain in infants that vary from adults but there is still strong evidence in the data confirming that infants are indeed processing the pain as an adult would. Given these results, Dr. Goksans hypothesis is supported and we should see changes in clinical pain management in infants.

These research studies are just a small example of how fMRI and overall the advancement in medical technology is helping us get a better understanding of what is going on inside our bodies so that way we can provide our patients that proper care they need.

ARTICLE: https://elifesciences.org/articles/06356

Circadian Rhythms and Alzheimer’s Disease

       People make excuses every day. Usually these excuses are connected to the notion that there isn’t enough time for certain tasks, but in reality it’s because they aren’t prioritized. We make time for the things we prioritize. We make time to brush our teeth and cleanse ourselves, because we realize that it is a necessity. We feed ourselves, because we realize we can’t go on without replenishing our bodies. However, a disconnect can be seen when it comes to the importance of getting a full night’s sleep. Sometimes people are guilty of compromising a full night’s rest for other tasks that they prioritize above sleep. We can see in recent literature, that sleep regulation is organized by a complex set of genes, neurons, and environmental conditions. Furthermore, we can see that offsetting this balance and throwing off the body’s circadian rhythm can lead to more adverse effects and diseases than we might expect.

            In Christine Dubowy and Amita Sehgal’s article, “Circadian Rhythms and Sleep in Drosophila melanogaster”, one of the conclusions they make is that circadian and homeostatic regulation of sleep are important for “establishing similarities between Drosophila sleep and sleep in mammals (Dubowy et al., 2017).” It is observed in the experiment that when flies are deprived of sleep, they exhibit unusual behavior and this can be attributed to humans as well. There are a lot of neurons and genes involved in this process. We have a core molecular clock and abiding by it provides us with the best outcomes. The scientists make it very clear that sleep plays a huge role in our lives and that environmental factors such as stress, temperature, or starvation for example disrupt this process. A phone can’t work unless it is charged. We are the phones in this scenario, and by depriving ourselves of a full charge we aren’t only taking away from our maximum potential, but actually hurting our odds of living a long full life.

In an article posted to Science Daily, named “Body clock disruptions occur years before memory loss in Alzheimer’s”, based on research done at Washington University in St. Louis, the importance of sleep is once again explored. This article focuses on how “similar circadian disruptions accelerate the development of amyloid plaques in the brain, which are linked to Alzheimer's (Washington University, 2018).” By not getting a full night’s rest or breaking up hours of sleep and not going fully into a REM sleeping cycle, humans are truly neglecting their health to a larger magnitude then they think. If amyloid plaque development fluctuates in terms of how much sleep a person gets, then it’s safe to say that it is very important that people should get enough sleep every night. The chaos of our busy days and the environments we surround ourselves in are slowly chipping away at the homeostasis that our body is constantly trying to reach. Regardless of if this is a subconscious or conscious action, a lack of sleep will eventually catch up to everyone who doesn’t prioritize this vital practice. There is so much pressure put on all of us to stay awake and excel in our every day lives, but the fragmentations seen in our sleep cycles due to outside factors from the environment are truly putting us at risk for much bigger issues.

References

Dubowy, C., & Sehgal, A. (2017). Circadian rhythms and sleep in Drosophila melanogaster. Genetics, 205(4), 1373–1397. https://doi.org/10.1534/genetics.115.185157

Washington University in St. Louis. (2018, January 29). Body clock disruptions occur years before memory loss in Alzheimer’s. ScienceDaily. Retrieved February 28, 2018 from www.sciencedaily.com/releases/2018/01/180129150033.htm