Magnetic Memory

By Emma Sims

Effective treatments for major depressive disorder have been in high demand since medieval times. Antidepressant prescription drugs first became available in the twentieth century, yet still are not effective for many patients and often cause multiple side effects. Alternative treatments such as electroconvulsive therapy (ECT) have lesser-known detrimental features. Some patients may experience memory loss and confusion, as Brenda Griffith describes in the Scientific American article, "Fighting Depression with Magnets." Griffith has tried over twelve different antidepressant medications and ECT, all of which brought negative side effects and no relief for her depression. Finally, Griffith began transcranial magnetic stimulation (TMS) as a last line of treatment and saw drastic improvements in her depressive symptoms.

The process of TMS involves an electromagnetic coil placed against the head of a patient, usually at a location specific to their condition. Repetitive TMS provides stimulation through induced electrical current in axons. While the process provides electrical stimulation in cortical areas, deep brain structures such as the hippocampus are inaccessible through TMS. Regions demonstrating increased fMRI connectivity with specific deeper cortical structures are not always the same as the outer cortex areas stimulated, meaning that locations directly above the targeted area do not necessarily correlate with what lies directly underneath them.

TMS is not only useful for lessening symptoms of depression, but also beneficial for strengthening memory ability. Dr. Joel Voss, a neurology researcher at Northwestern University, focuses his work on memory improvement and recently held a lecture at Loyola University Chicago on the manipulation of memory ability through TMS. Voss's study compares success of a spatial memorization task with measures of precision of a simple memory task. In older adults with declining memory, he compares both item recognition and source recognition. His results show that source memory significantly improved (by as much as 30 percent) in participants who received TMS treatment, and the memory increase remained relatively better up to one week later after initial treatment in experimental group participants. Voss chose to electrically stimulate the hippocampal-cortical network in order to best reach the hippocampus, as it is a deep structure and not easily accessible through TMS.

Overall, transcranial magnetic stimulation is becoming more successful and common in treating various cognitive abnormalities such as depression and memory-related disorders. However, TMS must be used frequently over a substantial time period in order to prove successful in patients. The cost of many treatments can range from $300-$500 and adds up quickly in its typical thirty to forty sessions. Medical insurance has been recognizing and covering TMS costs much more frequently than before, and hopefully will continue to become more affordable for individuals in order to greatly stabilize and improve their daily lives.

Sources:
- Joel Voss lecture
- Picture: https://en.wikipedia.org/wiki/Transcranial_magnetic_stimulation
- https://blogs.scientificamerican.com/observations/fighting-depression-with-magnets/

Enhancing Memory Consolidation

Dr. Ken Paller recently did a talk in regards to targeted memory reactivation (TMR) and sleep. Each of us spend about a third of our lives asleep. In the time we are awake, we are constantly learning new things and consolidating that information. In his study, Dr. Paller set out to see if TMR could actually improve learning by selectively encouraging memory reactivation during sleep. Sleeping naturally aids learning and every day we learn things that are important, and others that are not. What makes learning effective is repetition which we can do while awake, but it also occurs while we are sleeping. Dr. Paller discovered that subtle sounds played while sleeping can strengthen memories. Study subjects would learn a memory task that included an auditory component and would then sleep with electroencephalographic monitoring. The sounds were presented during sleep and when the subjects woke up, their memory was tested. General memory consolidation is a normal part of sleeping. However, with TMR, the consolidation mechanisms can be improved and specific memories can be reactivated during sleep to strengthen them. Paller also found TMR to provide an advantage for learning a specific skill, enhancing good habits, and improvement in a therapeutic setting.

The article “How the brain consolidates memory during deep sleep” by Iqbal Pittalwala of Science Daily also talks about the consolidation of memory during sleep. It opens up by stating that even though our bodies are not very active during sleep, our brain is. There are high frequency brain waves from the hippocampus and large amplitude, slower waves in the cortex. The memories we make throughout are day are initially stored in the hippocampus, and some are then progressively transferred to the cortex as long-term memory during sleep. Researchers from UC Riverside developed a computational model which demonstrated that synaptic changes affect the patterns of slow oscillations. This promotes a kind of reinforcement of specific firing sequences of the cortical neurons which represents a replay of specific memory. This can lead to increased learning and consolidation of memories in the brain. Their research found a mechanistic explanation for how memories are formed in the cortex and become independent of the hippocampus. By influencing these oscillations, the hippocampal input activates selective memories during sleep and causes a repetition or rehearsal of these memories. This relates back to Dr. Paller’s research since he used TMR to actually strengthen this effect and to target specific memories. The article states that when memories are rehearsed in the brain, the corresponding synapses are strengthened. Dr. Paller discussed the plasticity of the brain. The more you use a part of your brain, the stronger the synaptic network will become.

The research study along with this article demonstrate just how important sleep is for learning. There is an average of 4-5 alternating cycles of NREM and REM in an eight-hour sleep period. Therefore, it is important to get enough sleep so that we can effectively learn and form new memories. We now know it is even possible to improve recollection through the methods used by Dr. Paller involving TMR.

References:

https://www.sciencedaily.com/releases/2016/04/160414214830.htm

Alzheimer's Disease and Driving

It is self-evident that Alzheimer’s Disease (AD) is one of the most prevalent disease among the older population and also the fourth leading cause of death in the U.S, plaguing over 5.5 million people. It is projected that halfway through 21^st century the figure will rise to three times as many AD patients. Alzheimer’s also happens to be one of the saddest and worst kind of disease to be diagnosed with, as this disease attacks the hippocampal neurons in most patients, which results in patient losing their cherished memories. Dr. Roberto Fernandez’s study Early Alzheimer’s disease blocks responses to accelerating self-movement began by giving background information about the disease itself, he explained that this disease is most common in population older then 65 and is also the most common form of dementia. This disease has early symptoms of impairment of recent episodic memories; there is no cure yet, no preventative measure to slow the disease down, or even an effective method to diagnose or prescreen this disease. These are some of the reasons given by Dr. Fernandez’s introduction which outlines the importance of the research of the Alzheimer’s disease.

            Dr. Fernandez explained that AD occurs with presence and accumulation of Amyloid Beta plaques which serve as the hallmark of this disease as well as genetic risk factors, selective vulnerability, and why some group of people are predisposed at greater rate to AD. Dr. Fernandez’s study concentrates on relationship of the visual motion. Dr. Fernandez described exactly what his research has focused on by discussing the posterior cortical distribution of AD pathology. The reason why Dr. Fernandez chose to do this study was due to there being certain selective vulnerability of specific neuronal populations and the spread of pathological functional networks that are associated with the Alzheimer’s Disease. He specifically chose to perform detail study on the parietal lobe function and the perceptual base of navigation because it is very ideal to study in the aging population and the correlation with AD. Lastly, AD is known for its notorious association with the posterior cortical atrophy and this research focuses on those effects in the AD patients. 

            I greatly appreciated the way Dr. Fernandez set up his lab experiment. The experiment was set up in a visual reality driving test stimulation which was focused on the optic flow and the optic motion that is present during movement and self-movement. The visual reality driving test was tested and the test subjects were as followed: a younger group of subjects without the AD, an older group of subjects without AD, and finally another older group of subjects with AD. The study was testing what is known as Event Related Potentials (ERPs), which are accumulation of stimuli that result in firing of a neurotransmitter. The ERPs, involve horizontal moving dot patterns which induce a negative wave peaking at around 200ms and the driving simulations tested the presence of the N200 response. The results of the study were predictable and as hypothesized by Dr. Fernandez. There was a greater motion consistency and quicker optic flow which produced great N200 peaks; this was seen in the younger population because they did not suffer from the AD. However, the study proved that AD is involved in smaller optic flow and reduced N200 peaks in the older group of subjects with AD. It was also interesting to see that age difference had little effect on the N200 peaks as the both younger and older test subjects without AD had very little difference in their N200 peaks but compared to subjects who suffered from AD had significantly reduced N200 peaks.

            I also came across another study; Lack of sleep may be linked to risk factor for Alzheimer's disease: Preliminary study shows increased levels of beta-amyloid, however, there is currently less known about the impact in the human brain as this study was done on mice. As a student who has to stay awake for long periods of time due to studying for exams and other academic related work, it is a bit concerning and scary reading about this. The study gives new insight about potentially harmful effects of lack of sleep on the brain which tells us even more about the pathology of AD. This study was led by Dr. Ehsan Shokri-Kojori and Nora D. Volkow of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and Dr. Volkow who is also the director of the National Institute on Drug Abuse at NIH.

To understand the possible correlation between the sleep and Amyloid Beta build up, PET scans were taken from 20 healthy subjects ranging from age 22 to 72, after a night of rested sleep and then after sleep deprivation (being awake for about 31 hours). They found beta-amyloid increases of about 5 percent after losing a night of sleep in brain regions including the thalamus and hippocampus, regions especially vulnerable to damage in the early stages of Alzheimer's disease. However, the study does not answer whether the increase in Amyloid Beta may possibly subside following a night of rest. Although, this sample size was small for the demonstration of this type study but the preliminary assessments do point in the direction that there might be some correlation between sleep and Amyloid Beta accumulation.

            In retrospect of both studies, looking at Alzheimer’s Disease and the rate at which it is rising in population is scary and especially the detrimental effect it has on the people that are diagnosed with AD. It is evident that patients with late onset AD, are completely dependent on family and nursing homes to carry on day to day tasks. I learned from Dr. Fernandez that AD patients lose the ability to function in motion related tasks, which in his study concentrated on driving simulation. AD is a very pressing, important and aforementioned is in fact a very sad disease because patients are simply unable to take care of themselves which can have a huge emotional and physical toll on their loved ones and themselves. However, going back to the dynamics of the study which clearly showed the decrease in ability to drive safely in patients with dementia, it is of paramount importance to educate people and state legislations to take effective measures to prevent AD patients from driving after a certain time period in their disease state without stigmatizing them. This initiative will not only decrease the number vehicle related accidents of AD patients but also spread awareness about the disease itself.

 Work Cited 

1) Early Alzheimer’s disease blocks responses to accelerating self-movement

https://loyolauniversitychicago-my.sharepoint.com/personal/rmorrison_luc_edu/Documents/Forms/All.aspx?slrid=0b66629e%2D3002%2D5000%2Dcfcc%2D24d288cc413e&FolderCTID=0x01200052F973E683B96F4F97B49148A837C07C&id=%2Fpersonal%2Frmorrison%5Fluc%5Fedu%2FDocuments%2FNEUR%20300%2F%2803%2E27%2E18%29%20%2D%20Roberto%20Fernandez%2DRomero%2FNBA2012%2Epdf&parent=%2Fpersonal%2Frmorrison%5Fluc%5Fedu%2FDocuments%2FNEUR%20300%2F%2803%2E27%2E18%29%20%2D%20Roberto%20Fernandez%2DRomero

2) Lack of sleep may be linked to risk factor for Alzheimer's disease: Preliminary study shows increased levels of beta-amyloid

https://www.sciencedaily.com/releases/2018/04/180413155301.htm

3) https://www.cdc.gov/aging/aginginfo/alzheimers.htm

Losing Sleep Over Alzheimer’s Disease?

Losing Sleep Over Alzheimer’s Disease?

            While you probably know that not getting enough sleep can cause a number of health issues, did you know that not getting enough sleep could potentially increase your risk of developing Alzheimer’s Disease? A recent study done by the National Institute of Alcohol Abuse and Alcoholism, funded by the National Institutes of Health, suggests that “losing just one night of sleep [can lead] to an immediate increase in beta-amyloid, a protein in the brain associated with Alzheimer’s Disease” (NIAAA 2018).

            Twenty subjects, ages 22 to 72, underwent PET scans after a night of sleep deprivation (staying awake for 31 consecutive hours) and a night of ‘rested sleep’. Researchers were interested in a possible connection between beta-amyloid accumulation and sleep. It was found that “beta-amyloid increases about 5% after losing [just one] night of sleep in brain regions including the thalamus and hippocampus, regions especially vulnerable to damage in the early stages of Alzheimer’s Disease” (NIAAA). While future studies are needed in order to increase external validity, the findings have opened up another door that leads to a better understanding of the disease, and hopefully one day, a cure. Dr. Shokri-Kojori of the NIAAA says that this study “demonstrates the negative effects of sleep deprivation on beta-amyloid burden in the human brain.” While sleep deprivation seems to be a popular risk factor and symptom for many health problems, other symptoms such as trouble with visual processing and spatial cognition are common signs of early onset Alzheimer’s Disease.

Research done by Roberto Fernandez, MD, MPH, PhD, found that changes in beta-amyloid and tau can cause Alzheimer’s; however, he says the cause of these changes is still uncertain. Because Alzheimer’s effects certain parts of the brain before others, a gradual decline in patients’ function is seen as the disease progressively spreads throughout the brain. Up to one third of Alzheimer’s patients experience visuospatial deficits as early symptom (Fernandez). Perhaps sleep deprivation is the missing piece to the puzzle? If an immediate increase in beta-amyloid protein is associated to sleep deprivation, maybe Alzheimer’s can eventually be prevented or the progressiveness slowed down through more extensive research.

Research Study: β-Amyloid accumulation in the human brain after one night of sleep deprivation

http://www.pnas.org/content/115/17/4483 

Found on the site:

https://www.sciencedaily.com/releases/2018/04/180413155301.htm

Research done by Roberto Fernandez, MD, MPH, PhD:

https://loyolauniversitychicago-my.sharepoint.com/personal/rmorrison_luc_edu/Documents/NEUR 300/(03.27.18) - Roberto Fernandez-Romero/NBA2012.pdf