Circadian Rhythms Refresh the Brain

As everybody knows, sleep is important. When we don't get enough sleep we feel slower mentally, but when we get the right amount we feel sharp and on top of the task at hand. Now the normal person might say its because their eyes are heavy, but there is a deeper neurological process that causes these things. Dr. Emily Willingham in her article, "Sleep Deprivation Shuts Down Production of Essential Brain Proteins", focuses on the synapses and what occurs when our "clock" genes are not as they should be. 

Where these aforementioned genes primarily work is in the synapses. While working in the synapses prior to sleep, the genes are telling the cell to make proteins to help the synapse grow. One might ask, "How then does sleep play a role if the genes are active prior to sleep?". While the genes do work without sleep, they work at a much lower rate and are highly ineffective when one is sleep deprived. All the genes are doing is preparing the correct machinery to grow its synapses, not actually building the synapses itself. Later, Dr. Willingham talked about how, what she called, "sleep pressures" are the final step before the proteins become active.

Later in the article, we learn that the genes actually have two functions during the sleep wake cycle. Those two functions occur right before you go to sleep and right before you wake up. When falling asleep, the proteins shift their focus to building more proteins to help the synapse grow, but when waking, the proteins change their function from building to helping the synapse function. The researchers knew this was related to those "clock" genes, because when they looked at protein activity in regular mice compared to KO mice, which had deleted "clock" genes, they saw a difference. The regular mice had much higher protein activity in and around the synapse while the KO mice had little to none. To go along with the sleep wake cycle, proteins are being produced the most in the late evening and the early morning. This goes along with the idea that they have different functions at sleeping and waking.

The topic of sleep and total body function has always been something that is extremely interesting to me, and I never really understood how it worked. I always knew that when I don't get enough sleep I have a more difficult time functioning. Now it is known to me that not only do circadian rhythms play a role, but the genes and proteins that they produce. While sleeping is important to build the synapses and create more connections, waking up naturally helps the synapses function at a higher and more efficient rate, therefore making one more alert throughout the day. 



https://www.scientificamerican.com/article/sleep-deprivation-shuts-down-production-of-essential-brain-proteins/

Are Brain Games the Optimal Cognitive Impairment Treatment for Schizophrenia?

According to MedicalNewsToday, progress has been made in regard to identifying potential methods of cognitive remediation in patients with schizophrenia. Schizophrenia is a condition where those who develop symptoms, usually in their late teens to their late twenties,  suffer from delusions, disorganized speech, disorganized behavior, hallucinations, or other negative symptoms for a functional impairment period of at least 6 months. Targeted Cognitive Training, or TCT, is one implemented method used to attempt to rectify the cognitive hurdles that those with schizophrenia may experience. Scientists such as Gregory A. Light, Ph.D found success when he approached a group of chronic, treatment-refractory patients who had previously been hospitalized due to their conditions by enrolling them in a TCT program. This involved using a laptop with the program over the span of three months. After this period, hallucinations decreased and verbal learning abilities improved significantly, leading to the assumption that cognitive exercise such as TCT seems to be effective in treating cognitive abilities in schizophrenic patients. 

On February 18th, 2019 Dr. Molly Erickson presented at Loyola University of Chicago to discuss her research also regarding patients dealing with schizophrenia. Specifically, her research was interested in a potential source of the impeded cognitively ability closely tied with the development of schizophrenia, which she believed to be in the encoding and consolidation process of working memory.  Originally, methods like computerized-cognitive training, such as the commonly known program Luminocity or TCT, were utilized in attempts to maintain or improve and maintain the healthy cognitive function as well as those suffering from some sort of cognitive impairment, such as the kind that may develop with people who develop schizophrenia. 

While this method has seen some improvement and effectiveness in helping schizophrenic patients get more adept at certain cognitive tasks, working memory-based problem solving is one region where things such as Luminocity and TCT still fell short. When Dr. Erickson and her team took a closer look at alpha-dynsynchronization and beta-desynchronization behavior during cognitive processes in working memory they found that when they allowed for schizophrenic patients to practice and exercise alpha-desynchronization in regard to a graphic image, essentially training themselves to exercise that cognitive muscle, that their working memory improved. Alpha-desynchronization is believed to have a potentially causal role in working memory capacity, thus improved working memory capacity was observed after patients were given the opportunity to remediate with more permanent effectiveness than computerized-cognitive training.

Sources

Erickson, M. A., Smith, D., Albrecht, M. A., & Silverstein, S. (2019, July 18). Alpha‐band 

desynchronization reflects memory‐specific processes during visual change detection. 

Retrieved February 22, 2020, from 

https://onlinelibrary.wiley.com/doi/pdf/10.1111/psyp.13442

Sandoiu, A. (2018, December 9). This form of brain training may help treat severe 

schizophrenia. Retrieved February 22, 2020, from 

https://www.medicalnewstoday.com/articles/323933 

URL of Article:
https://www.medicalnewstoday.com/articles/323933#TCT-reduces-hallucinations,-boosts-learning

PTSD, ADU & Gender

     In Dr. Amy Herrolds paper, “Alcohol use and craving among Veterans with mental health disorders and mild traumatic brain injury,” her and her colleagues examine self reported alcohol craving among Veterans that were previously deployed overseas with active mental health disorder (MHD) symptoms and with or without mild traumatic brain injury (mTBI) symptoms. These reports were compared to self reported alcohol craving in healthy, asymptomatic veterans. The results reflected that Veterans with active MHD symptoms with or without mTBI symptoms self- reported higher alcohol craving than the healthy, asymptomatic veterans. In the study, 44 out of 48 participants were male. This led me to wonder if demographic plays any roll in PTSD and Alcohol use disorder, specifically gender.

     Dr. Emily Dworkins, and colleagues, work, “Co-Occurring Post-Traumatic Stress Disorder and Alcohol Use Disorder in U.S. Military and Veteran Populations”, analyzed the impacts of demographic on differential risks for PTSD and AUD. Dworkin found that there was a higher prevalence of PTSD in female veterans, 13- 19%, than in male veterans, 6-7%. This is likely due to the sexual assault of women in the military. About 22% of women in the military report they have been sexually assaulted, whereas only 1% of men in the military report they have been sexually assaulted. 

     Although men in the military report lower numbers of PTSD and sexual assault, they report more binge drinking in the past month than their female counterparts do. A possibility for this is the drinking culture associated with the military. Drinking is a bonding, recreational and stress relieving experience and can influence the perception of alcohol consumption norms. Military drinking culture has a large effect on Alcohol use in veterans because it is normalized as a way to relax that carries k err into life after service.

     In studies generalizing to the entire military, it would make sense for there to be an over representation of men just as there is in the Armed Forces, similar to a stratified sample where the subjects representation in the study is proportional to the representation in the population of interest. While gender does play a role in the prevalence of PTSD and alcohol use disorder, when making a statement generalizing to the U.S military rather than the entire U.S population, the differences caused by gender are negligible due to the over representation of men in this population.

Dworkin , Emily R, et al. “Co-Occurring Post-Traumatic Stress Disorder and Alcohol Use 

Disorder in U.S. Military and Veteran Populations.” 2018.

Herrold, Amy A., et al. “Alcohol Use and Craving among Veterans with Mental Health

Disorders and Mild Traumatic Brain Injury.” Journal of Rehabilitation Research and Development, vol. 51, no. 9, 2014, pp. 1397–1410., doi:10.1682/jrrd.2013.07.0170.

Recent Advances in Understanding Cognitive Impairment in Schizophrenia

People with schizophrenia have a wide range of positive and negative symptoms including delusions, hallucinations, fatigue, emotional inexpressiveness, and impaired cognitive functioning. The medications commonly prescribed are mostly targeted to treat the positive symptoms (hallucinations, delusions), but the side effects tend to worsen some of the negative symptoms and don’t even touch cognition impairments.  Recently, more research has been done to investigate the impairments and mechanisms driving these cognitive impairments such as poor memory.

In 2016, the article, “Brain marker of poor memory in schizophrenia patients identified”, from ScienceDaily came out. In this article, the author describes research performed to expand on previous fMRI attempts to see if the dorsolateral prefrontal cortex (DLPFC) is directly involved in the cognitive memory impairments seen in schizophrenia patients. Though the research has been done before, no conclusive evidence was found to support this idea. This time researchers proposed that there may not have been differences because the test administered did not have enough levels of difficulties for the memory tasks. This would imply that in normal memory functioning, there may be a gradual activation or a necessary threshold at some point in the memory task for the DLPFC to activate significantly. If the research prior to this study did not reach that threshold or have enough difficulty levels to compare against in healthy individuals, this would explain not seeing any significant changes in the DLPFC between the control and schizophrenia groups. 

In the recent study, they had healthy individual controls, medicated schizophrenia patients, and nonmedicated schizophrenia patents. Each group underwent single word memory tasks while undergoing fMRI imaging and the memory tasks had eight levels of difficulty. The results showed significantly less activation both schizophrenia groups compared to the healthy individuals. The lower activation corresponded to difficulty with the memory tasks. This was the first study to identify the DLPFC as brain marker for one of the cognitive impairments in schizophrenia patients. The findings are a great step in the right direction but questions still remain to be answered. Why is the DLPFC responsible for this impairment? How is the DLPFC regulated in schizophrenia patients as opposed to healthy individuals? Hopefully advances in this field continue to bring insight to this issue.  

Citation: Columbia University Medical Center. (2016, April 4). Brain marker of poor memory in schizophrenia patients identified: Possible key to understanding, treating cognitive symptoms of disease. ScienceDaily. Retrieved February 22, 2020 from www.sciencedaily.com/releases/2016/04/160404143843.htm

URL: https://www.sciencedaily.com/releases/2016/04/160404143843.htm

PTSD and MDMA

              PTSD has affected the lives of countless of individuals following traumatic experiences that continue to haunt them. Treatment for PTSD using drugs has remained generally unchanged for the past 17 years. The leading treatment for PTSD is psychotherapy with supplemented SSRIs to treat symptoms of depression. However, SSRIs fail to relieve the individual of sensations of immediate peril when they are outside of the safety of their home, and many patients suffering from this disorder seclude themselves as a result. While isolation would appear to be a symptom of depression, treatment with SSRIs does not help the patient feel safe enough to reintegrate with society without the risk of encountering triggers of the past trauma.

              New research has emerged which suggests MDMA paired with guided psychotherapy can solve this issue. With this new method, patients will come to a twelve-week course of eight to twelve hour sessions of therapy while using a carefully controlled dose of MDMA. Then there is a follow up session without the influence of the drug to assess the patient’s experience and thoughts while on the drug. Since MDMA releases serotonin and oxytocin, feelings of social connection can arise. When this drug is paired with guided psychotherapy, the patient can revisit their traumas with new feelings of empathy, closeness, and safety. Among the first trials, researchers found a 54% rate of remission in patients with PTSD such that patients no longer fit the criteria for PTSD after one year of therapy and even higher rates after two years. Researchers claim that since the patient is not prescribed to take the drug at home but rather in a controlled psychotherapeutic environment, there is little risk of abuse with the drug.

              In the article ‘Transcranial magnetic stimulation: potential treatment for co-occurring alcohol, traumatic brain injury and posttraumatic stress disorders,’ Dr. Amy Herrold et al. examines the prevalence of alcohol use and craving with comorbid mental health disorders and mild traumatic brain injury among a group of Veterans. The frequency of these co-occurring disorders is astounding and something not previously studied until now. Veterans that have seen combat suffer from brain injuries as well as lasting psychological distress, and attempt to self medicate using alcohol in lieu of effective pharmacological treatment. Her findings suggest that transcranial magnetic stimulation could pose potential benefits for these co-occurring disorders. The answer to this treatment’s effectiveness lies in its ability to treat a brain region common in all disorders, such that when a patient comes in displaying symptoms of all three they are able to treat them with one type of treatment.

What both of these studies comprehend are modern and innovative techniques for a disorder long seen as incurable. Both are non-invasive treatment options for those with which no other methods of therapy have proved effective. The implications of these studies show a promising future for those who have long suffered from their traumas, giving hope in their ability to move on and reintegrate with society.

Herrold AA, Jordan N, High WM, Babcock-Parziale J, Chambers RA, Smith B, Evans CT, Li X, Mallinson T, Jenkins S, Pape TL. Alcohol use and craving among Veterans with mental health disorders and mild traumatic brain injury. J Rehabil Res Dev. 2014;51(9):1397-1410. http://dx.doi.org10.1682/JRRD.2013.07.0170

Herrold, A., Kletzel, S., Harton, B., Chambers, R., Jordan, N., & Pape, T.-B. (2014). Transcranial magnetic stimulation: potential treatment for co-occurring alcohol, traumatic brain injury and posttraumatic stress disorders. Neural Regeneration Research, 9(19), 1712. doi: 10.4103/1673-5374.143408

Stone, W. (2019, August 21). MDMA, or Ecstasy, Shows Promise as a PTSD Treatment. Retrieved February 20, 2020, from https://www.scientificamerican.com/article/mdma-or-ecstasy-shows-promise-as-a-ptsd-treatment/

PTSD and Ecstasy Treatment

          On the 21^stof January, Amy A. Herrold presented her work on the relationship between PTSD in veterans and the use of alcohol. She focused on veterans as her test subjects as they commonly suffer from PTSD. Her studies displayed the heightened level of alcohol cravings in these individuals that have returned from war. 

          After reflecting upon this study and the fact that alcohol is classified as a depressant, I was curious to see if a stimulant drug would produce a different effect. I came across an article that focuses on the effects of MDMA, otherwise known as ecstasy, that was used as a treatment for patients with PTSD. This article, titled “PTSD and Ecstasy: Science and Perception” was published in Psychology Today, describing the work of Michael Mithoefer. 

          PTSD is a mental health disorder that can occur after someone experiences a traumatic event in their life. They may suffer from anxiety, depression, or a multitude of other similar disorders. Common treatments consist of antidepressant or anti-anxiety medication, but some individuals have not received the level of alleviation desired and still struggle with their disorder on daily basis. 

          Mithoefer gathered 26 individuals suffering from PTSD and separated them into three groups that varied based on MDMA dosage: 30mg, 75mg, 125mg. These individuals also were subjected to psychotherapy sessions post MDMA treatment. In addition, subjects were asked to participate in weekly phone calls to evaluate their treatment and progress. Upon evaluating the data collected, it appeared that the subjects that were given the two highest doses of MDMA experienced a dramatic decrease in symptoms. Out of the 26 subjects, 24 individuals remained in the study throughout its entirety and did not experience any serious side effects. 

          While the details concerning the means of MDMA’s effects are unclear, research has explained the serotonergic activity that occurs within the brain. Combined with psychotherapy, MDMA has shown very positive effects on treating patients with PTSD. While it remains that more testing needs to be conducted, this study presents a fascinating discovery about the use of this psychedelic drug. This study could provide a life changing treatment to those who are battling with PTSD and give them the opportunity to gain their lives back. 

PTSD and Ecstasy 

Rubin M.D., Ph.D, Eugene (2018, October 3). PTSD and Ecstasy: Science and Perception. 

          Psychology Today. https://www.psychologytoday.com/us/blog/demystifying

          psychiatry/201810/ptsd-and-ecstasy-science-and-perception

PTSD and Alcohol

https://www.dropbox.com/s/rhxnm57kzz7zywo/neuro300_syllabus_Spring20.pdf?dl=0

TMS and other neurological disease states

In 2017, an article in the New York Times called "New Electrical Brain Stimulation Technique Shows Promise in Mice" was published. In this article, Pam Belluck spoke of a cutting-edge new approach that she believes can aid patients that are suffering from Parkinson's disease, OCD, depression, and more. This is due to something called "temporal interference." In temporal interference, electrical impulses that can be administered at different frequencies. They found that if they administered frequencies that are too high and fast, the neurons will thus not be able to respond to them. However, at the location where the currents crossed paths, the neurons responded. This is because if there are two high frequency currents intersecting, they will cancel each other out and only the difference will be left. This differs from TMS, which is talked about in Amy Herrold's paper, because it does not affected ay surrounding areas in the brain. It allows scientists to pinpoint a certain location that they want to specifically target.

In Amy Herrold's research paper, she proposed that TMS is a somewhat effective method in which AUD, PTSD, and depression can be treated. She concludes, however, with the suggestion that more research on humans must be done to see the final results.

Both of these methods are very interesting because they are both non-invasive treatments that can potentially treat neurological and neurodegenerative diseases that are not commonly an easy fix for patients. On the other hand, they both also have complications in their administrations and long-term affects. For temporal interference, it is hard to treat complex diseases such as Parkinson's because that would require constant electrical stimulation, which can be difficult to manage. For TMS, the diseases that Herrold was talking about are difficult to measure due to methods of determining depressive states can be highly subjective.

Regardless, of those issues, I think that it would be great to conduct more research and gather more data in order to find how these two methods can be used to potentially help neurological diseases that have yet to have a legitimate cure.


Article about temporal interference:
https://www.nytimes.com/2017/06/01/health/new-electrical-brain-stimulation-technique-shows-promise-in-mice.html?searchResultPosition=8

Amy Herrold's paper on TMS and co-occurring neurological diseases:
https://www.dropbox.com/sh/hdluh1vfs2cphhz/AABHUOxPAP_XWzl0AL7lWWzga/(01.21.20)%20-%20Amy%20Herrold?dl=0&preview=Herrold+2014+Neural+Regeneration+Research+TMS+Review.pdf&subfolder_nav_tracking=1