Wednesday, December 12, 2018

TMS: What has been long considered a controversial treatment is now looking to be one of our best options.

Over 60 million people, globally, suffer from epilepsy which is “a neurological disorder marked by sudden recurrent episodes of sensory disturbance, loss of consciousness, or convulsions” and its associated seizures, which are caused by associate abnormal electrical activity in the brain, making their day to day lives more difficult than we can ever imagine. Many different therapies have been widely used in aiming to help with this illness. 

Two technologies that have helped in the advancement of making the lives of those who experience seizures caused by epilepsy are Deep Brain Stimulations (DBS) and Transcranial Magnetic Stimulations (TMS). Professor Hui Ye also discussed this when he led his talk. To dive more into depth on the two types, historically, DBS has been used in helping to treat different control illnesses such as side effects caused from diseases like Parkinson’s. DBS has been expanded to now help with different causes, those including nicotine depression and suicide. In DBS there are electrodes that are implanted behind the patient's ears and are connected via a wire to a neurostimulator which is embedded within the chest. Typically patients are given a remote control that they use to turn on and off the machine to simulate electrical charges. Although this method has proved useful in the past because it is a surgery there are many complications associated with it including infection or internal bleeding. Side effects after the implantation are also possible including hardware complications or possible swelling at the site. 

Transcranial Magnetic Stimulation (TMS) is a treatment, however, that is non- invasive, non- drug that uses magnetic pulses to stimulate parts of the brain. It has been used as a therapy to help with multiple different issues including helping someone quit smoking or helping someone who is depressed. In the past, it has been helped to treat patients with depression by simulating the pulses to areas that are underactive in depression such as the prefrontal cortex.  For epilepsies and seizures, the area of the brain involved most likely is in and around the hippocampus. “In recent years, rTMS, particularly low frequency (0.3 to 1 Hz) rTMS that can induce a lasting reduction in cortical excitability, has emerged as a potential treatment for intractable epilepsy”.Professor Ye’s talk gave an interesting look into his research where the goal was to investigate the neurological mechanism of magnetic control of seizure to facilitate its clinical implementation.  

As research is showing, there is a new technology available with less side effects, being less invasive that is a new and upcoming field, and we should start to take advantage of it!

Works Cited:

NOOHI, Sima, and Susan AMIRSALARI. “History, Studies and Specific Uses of Repetitive Transcranial Magnetic Stimulation (RTMS) in Treating Epilepsy.” Iranian Journal of Child Neurology, Winter, no. 10, 2016, pp. 1–10. i.

Pages, Kenneth. “TMS Can Help Patients With Depression.” Psychiatric News, 17 Nov. 2017, psychnews.psychiatryonline.org/doi/full/10.1176/appi.pn.2017.pp11b3.

Rotenberg, Alexander. “Prospects for Transcranial Magnetic Stimulation in Epilepsy.” Prospects for Transcranial Magnetic Stimulation in Epilepsy, Epilepsy Foundation, 2 Dec. 2015


Theodore, William H. “Transcranial Magnetic Stimulation in Epilepsy.” Epilepsy Currents: Reviews and Critical Analysis, vol. 3, no. 6, Nov. 2003, pp. 191–197.

Risky Behavior & Adolescence



            There has been quite a bit of research involving the exact causes and effects of ethanol and alcohol on the brain. In Dr. Roitman’s lecture, he specifically focused on the effects of alcohol consumption on risk and reward behavior by looking at the prefrontal cortex (PFC) and orbitofrontal cortex (OFC). The PFC is associate with higher cognition such as working memory and executive control over things such as goal-oriented behavior, behavioral flexibility, impulsivity, risk, patience, and inhibitory control. It is also important to note that the PFC matures during adolescence to dictate things such as physical development, social development, increased myelination, pruning of excitatory synapses, and proliferation of inhibitory circuits.
Roitman’s lab had previously found that the level of OFC activity post either risky or certain rewards would depend on the size, probability, and personal preference for that reward. In the researcher’s newest study, they assigned rats one of two conditions: alcoholic jello shots or nonalcoholic jello shots. Each rat was given two levers to choose from: one associated with a small, but certain payoff, and the other associated with a potentially large, but risky payoff. In their experiment, the data demonstrated that alcohol consumption in adolescents results in increased risky behavior in adulthood, which also were concurrent with altered patterns of activity in the OFC. In the absence of uncertainty, choice behavior was unaffected by adolescent intermittent ethanol (AIE) consumption. The researchers deducted that the altered OFC neuronal population shown in the rats that were the AIE rats could be experiencing heightened inhibitory interneuron release. The reduced level of activity in the ethanol high rats may be releasing inhibition on the excitatory projections from the OFC to reward circuitry enhancing dopamine signaling. In their article, the researchers also discussed how the differential patters of alcohol consumed by the alcohol high and low animals is telling of neurophysiological differences, potentially originating from adolescent development.
 The neurophysiological differences were almost exactly what researchers in New Zealand and California were studying. An analysis was conducted that found children whose “temperament was deemed ‘undercontrolled’ at age three were more than twice as likely as well-adjusted kids to have problems with gambling at age 21 and 32,” which is a risk-taking behavior (Time). Researchers have yet to confirm, but have speculated, that one possibility for these children to be at higher-risk is that there are genetic factors related to these behaviors or that these children tend to associated with other undercontrolled children who then manifest and increase these risky behaviors. The article then goes on to state that:
“An earlier analysis of the Dunedin population found that children with the most undercontrolled behavior at ages 3 and 5 had more than three times the risk of becoming addicted to multiple drugs as young adults, compared with those who had exhibited the highest levels of self-control.”
Combining these results with the results from a California study, they found that it was actually the youths that had the best behavior as preschoolers tended to use marijuana moderately in adolescence but had no issues controlling it. The director of the division on addiction at Harvard Medical School explained that:
“This means that treatment for gambling or substance problems cannot focus solely on the addictive behavior. “Clinicians must address the full spectrum of issues that tend to cluster with disordered gambling. It is not enough to focus exclusively on gambling activities. Key player attributes will need attention as well,” says Shaffer.”
These findings once again suggest that there is a multifaceted cause and multifaceted effects of addiction and risky behavior.
            Considering the findings from both the article by Time Magazine and Dr. Roitman’s research, the combined implications of risk-behavior and alcohol is that there is not one true way to pinpoint and predict this sort of behavior. There are many factors that will exponentially increase the likelihood of this behavior such as adolescence alcohol consumption with the OFC and PFC are still developing, childhood behavior, and genetic factors. Future research and any attempts to help this sort of behavior should focus on considering all of the factors and the way that they cumulate together to affect the individual.

Works Cited

@maiasz, M. S. (2012, April 26). Can Addictive Behaviors Be Predicted in Preschool? Retrieved
Mcmurray, M. S., Amodeo, L. R., & Roitman, J. D. (2015). Consequences of Adolescent
Ethanol Consumption on Risk Preference and Orbitofrontal Cortex Encoding of Reward. Neuropsychopharmacology, 41(5), 1366-1375. doi:10.1038/npp.2015.288


Transcranial Magnetic Stimulation and Epilepsy

Epilepsy is a neurological condition resulting in abnormal behavior such as seizures, loss of sensation or alternation of mental status. Epilepsy, unfortunately, can happen to anyone and the cause of this condition remains unknown. Undoubtedly, whatever defects our mental health as well as our life quality must be inhibited.

One of the most common treatments for epilepsy is taking anti-seizure medications, which can stop seizure right away… but not to everyone. Also, as you might guess, they always have side effects such like thinning bones, dizziness, trouble talking etc. Another option is deep brain stimulation which basically implants electrodes in several specific regions of your brains. Apparently, those are the ones having abnormal activities which will be adjusted by electrodes. The good thing is this treatment has been approved by FDA which can also applied to treat depression, stroke recovery, addiction. On the other hand, no one would like anything inserted into their body, especially the brain. Moreover, this procedure is usually expensive and of course risky. On the same token, Transcranial Magnetic Stimulation (TMS) is another advanced brain-stimulating method which is non-invasive because it utilizes the magnetic field generated by an external mini coil, followed by the induction of electrical currents in target region within the brain. It is considered a consistent stimulating technique since the intensity of magnetic field is less attenuating.

Back to 2014, the first attempt to implement TMS in investigating the mechanism of epilepsy was conducted by Dr Jancke from Ruhr-Universitaet-Bochum in Germany.  They administered voltage-sensitive dyes on the cell membrane. Under electrical stimulation induced by high-frequency TMS, the fluorescent signal would be detected inferring whether the neurons of interest are activated or inhibited. 

Those previous studies, when the neuron is considered to be polarized by electrical stimulation, it is one-way direction. In contrast, Dr. Hui Ye at Loyola University Chicago, who have been studying external-applied electric field to enhance therapeutic benefits of TMS, believes that the interaction between neuronal tissues and electrical field is bilateral. “A direct consequence of the counter-effects of the cell to the electric field is that electric field alteration by one individual cell may cause secondary effects on neighboring cells during electric stimulation, particularly in the scenario that two or more cells are located in close proximity and in a high-density cell medium” is one of his major findings. In addition, he also found that some features of magnetic field applied to induce transmembrane potentials of the hippocampal tissues include orientation, magnitude, frequency. On the same token, several neuronal properties such as the neuronal density and spatial organization within the tissues determine how strongly induced transmembrane potential (ITP) within a single neuron.

In order to improve the future study on ITP, Dr. Ye and his co-author suggest that the neuronal shape, radius, orientation and geometrical properties should be examined thoroughly. They believe that those properties could re-distribute the external field and determine the neuronal activity of electrically-targeted tissues. Dr. Ye suggests these parameters are important to build biophysics-engineering model of behavior of inhomogeneous tissues under the presence of external field, which might one day help us explain the mechanism of epilepsy.

Source:


Ye and Steiger  Journal of NeuroEngineering and Rehabilitation  (2015) 12:65


Unraveling America’s Gross Appetite




Unraveling America’s Gross Appetite

     Over the past decade, Americans have put on more weight. Research shows that “nearly 40 percent of [American adults] were obese in 2015 and 2016”, and that the numbers are on a “sharp increase” (Ritchel and Jacobs). Simply put, obesity is a condition of excess body fat. Medically speaking, an individual is considered to be obese when they weigh over 20 percent of their ideal body weight (given their BMI). Typically, Leptin --an “adipose-derived ‘satiety hormone”-- curbs our appetite, preventing us from overeating. However, recent data suggests that there has been a drastic change within our conserved system. With adult weight gain on the raise, a number of neurologists have set out to uncover the link between appetite and the neurological system.

     In her research, Dr. Jen Beshel and her colleagues at Loyola University Chicago, used Drosophila melanogaster (fruit flies) to investigate the brain’s feeding pathways. Within Beshel’s presentation, Using drosophila to Unravel the Neural Systems Controlling Food Intake and Appetite, she describes how the manipulation of fat tissue (specific for the GAL4 system) affected food intake, food odor attraction, and overall weight. In these experiments, Dr. Beshel utilized two different groups of fruit flies: starved and fed. The starved flies were found to be very attracted to food odor; whereas the fed flies were not. Seeing as how manipulation of fat tissue outside of the brain resulted in a knockdown of Upd2 protein -- causing a decrease in weight, with no effect on food intake or odor attraction-- Beshel and colleagues turned their study toward Upd1. They discovered that the unpaired 1 protein (Upd1) --a glycol-protein-- was expressed within the brain. Thus, by reducing the expression of neural Upd1 (knockdown), several hallmarks of obesity were exhibited; the most notable being an increase in food attraction. After suppressing the expression of Upd1 in the fed flies, Beshel was able to change their behavior to mirror that of the starved flies. In other words, the fed fruit flies (whom were originally non-reactive to the food odor) became very attracted to food odor. The same observation was noted in the food intake; thus, these fed flies were now eating more food.









In the second half of Beshel’s experiment, her lab examined the association between neuropeptides and weight gain. Utilizing a cohort of rodents, it was discovered that food deprivation resulted in an increase in neuropeptide Y (NPY) activity and foraging. Applying these results to her Drosophila experiment, Beshel’s lab surveyed the relationship between neuropeptide F (NPF) and weight gain. They discovered that not only was NPF necessary for food attraction, but that it was essential to accurately predict food behavior. When the food receptors were knocked out, the starved flies group did not react to the smell of their favorite food (foraging decreased). These result was attributed to the fact that NPF acts a novel processing stimuli. Therefore, those flies with the NPF domeless knockdown displayed the hallmarks of obesity (increased weight, food intake, etc.). Taking her analysis a step further, Beshel placed the flies on a high fat diet to mimic the diet of many Americans. It was discovered that the genetic perturbations in Upd1-NPF (a leptin analog) axis, lead to a “hypersensitivity to obesogenic conditions” (Beshel). In essence, the modifying and suppression of Upd1 resulted in a leptin resistance within the Drosophila. This leptin resistance in the neural pathway, caused the flies to eat more --in turn gaining more weight.  
In the Huffington Post article, Is Obesity a Self-Fulfilling Prophecy?, the authors discuss the results of a recent psychological study carried out by Florida State University. In the study, psychological scientists Angelina Sutin and Antonio Terracciano looked into the relationship between self-stigmatization and obesity. In other words, do teens who “embody the caricature of a fat person, literally grow into that caricature?” (Herbert). Utilizing data from the National Longitudinal Study of Adolescent Health, a cohort of 6,000 normal weight 16 year old participants (based on BMI) was analyzed. At the conclusion of the analysis, it was found that a majority of the teens who had “distorted perceptions of themselves actually became obese at age 28”. Likewise, “the fit teens who saw themselves as fat had a whopping 40 percent greater risk of being obese at 28, compared to fit teens with accurate perceptions”. The inability to perceive their bodies accurately, caused these teens to become “prone to extreme dieting practices”; as well as “internalized weight biases” which can lead to a decrease in self-control (Herbert). Although Sutin and Terracciano’s study looks at obesity from a psychological perspective, the data from their research is connected with that of Beshel’s.
The research outlined in Beshel’s talk, as well as the research conducted by the scientists at Florida State, demonstrate the important interplay between the brain and environment. Likewise, both studies suggest that obesity and weight gain can be the result of an undiscovered predisposition (whether genetic or psychological). There are several consequences associated with obesity, the most notable being an increased risk of heart attacks and heart disease. Though we now know the role of upd and Leptin in appetite, hopefully future studies can break the cycle of weight gain and uncover the direct link to obesity.

Works Cited:

Herbert, Wray. “Is Obesity a Self-Fulfilling Prophecy?” The Huffington Post, TheHuffingtonPost.com, 8 Mar. 2015, www.huffingtonpost.com/wray-herbert/is-obesity-a-self-fulfill_b_6424336.html.
Richtel, Matt, and Andrew Jacobs. “American Adults Just Keep Getting Fatter.” The New York Times, The New York Times, 23 Mar. 2018, www.nytimes.com/2018/03/23/health/obesity-us-adults.html.





Microglia, Macrodifference


Eyo and Dailey's review Microglia: Key Elements in Neural Development, Plasticity, and Pathology analyzed data from various studies on microglial cell function and behavior. It provided a comprehensive account of the role of microglia in the damaged central nervous system, detailing their involvement in a wide span of processes relating to development, behavior, pathology, and, potentially, therapeutics. I was particularly interested of the role microglia may play with respect to the immune system, as this seems to hold the most potential in treatment of some of the most challenging and common neural diseases.
Microglial cells are lauded as the immune cells of the nervous system. Their engagement and clearance of cellular debris and cells that are damaged or infected attests to their functional capabilities as phagocytes. Eyo and Dailey cited observations of microglial engulfment of presynaptic material in the developing nervous system, as well as in vivo studies of leech, goldfish, rat, and mouse specimen as further evidence of this immune-related function of microglia.
It is known that early on in prion infection, microglia and astrocytes become activated prior to neural damage or death. A news release by the National Institutes of Health, "Microglia are key defenders against prion diseases" further supports the notion that microglia provide defense against infection. The paper describes the promising research findings of Carroll and colleagues, whose work with experimental drug PLX5622 showed that decreasing microglial activity resulted in heightened prion disease progression. The information from this study, Microglia are critical in host defense against prion disease, proves promising in terms of treatment development, as it reveals the potential for drugs to slow prion disease progression by assisting microglia in their defensive role.
The review by Eyo and Dailey also turned attention towards studies on zebrafish as recent areas of progress in the understanding of microglial behavior, especially as it relates to immune function. Due to optical transparency and considerable characterization of the zebrafish developmental system, which bears similarities with that in humans, this specimen has been an excellent model for demonstrating microglial phagocytosis.
One study that has made use of the zebrafish model is that conducted by Wen Zilong and colleagues at the Hong Kong University of Science and Technology. This research lab is the largest zebrafish research facility in Hong Kong and primarily focused on the cellular and molecular basis of macrophage development and the roles of microglia in organ development and tissue regeneration. By studying the developing brain in zebrafish, it has been able to gain insight into the development of neurodegenerative disorders and recently encountered a breakthrough finding. Using light-induced mapping technology, it has observed a relationship between microglia and dementia vulnerability. This finding could help further medical developments to mediate and potentially delay the onset of diseases such as Alzheimer's and Parkinson's. It is yet another testament to the promising trajectory of the study of microglia, both in the understanding of neuropathology as well as treatment.



The Role of Microglia in the Brain

As more and more research is being done on the brain and its structures, we are discovering that there may be more significant elements that play key roles in its function than previously thought. One of these elements is microglia. Apart from its commonly known role as the scavengers of the brain and one of its first lines of defense, microglia are also involved in inducing cell death, promoting tissue repair, and other types of development. Many research studies are underway to explore these seemingly newfound functions of microglia that are specifically focused on how they are involved in development, repair, and diseases in the brain.
One research study done by Ukpong B. Eyo and Michael E. Dailey looks at the role of microglia. In this study, the researchers look at microglia as the often overlooked ‘3rd element’ of the nervous system working alongside other key structures such as neurons and astrocytes. In the article Microglia: Key Elements in Neural Development, Plasticity, and Pathology, it details microglia as having a wide range of functions in the brain including migrating to injuries, induction of cell neuronal death, phagocytic clearance of cellular debris, the monitoring of the functional states of synapses. One particularly significant point the article mentions is that it was previously thought that in uninjured brain tissue microglia were nonmotile. This notion was later overturned with the discovery that even in healthy tissue, the microglia are very motile just not migratory. This discovery means that microglia in the “uninjured adult CNS are motile, non-migratory cells functioning to persistently survey the CNS to detect aberrations”. Though they do respond to injuries in brain tissue, even in normal tissue, they are not simply stationary and inactive. Furthermore, this leads to the idea that microglia are not just activated when there are injuries in the brain they actually have proactive role in the maintenance of the brain that was previously not known.
Similarly, another study ,detailed in the article Rise of the Microglia, discusses the work of the researchers at the European Molecular Biology Laboratory and their study on microglia. This article talks about another newly discovered function of microglia which is their role in synapse sculpting. This means that as the brain is developing in vivo, microglia are critical to this process as they “they gobble up synapses, thus helping to sculpt the brain by eliminating unwanted connections.” Though this provides important insight into the development of the brain, it also raises questions about what can occur if this sculpting process goes wrong. Specifically, the article mentions that “studies have also found evidence for increased microglial activation in individuals with schizophrenia and autism” though the exact cause behind these disorders are unknown. This means that microglia could possibly be looked at in terms of assessing reasons for a certain disease and even potential treatments for them. By understanding that these structures have a key role in development, it brings to light the fact that there is so much that still may be unknown about how the brain develops.
When looking at and comparing these two studies, it is important to think about how recent so many of these discoveries are. Previously, the functions that are not attributed to microglia were most likely not fully understood or were overlooked. There are so many aspects of the brain and nervous system that scientists still do not completely understand, leading to the idea that there may be other structures in the brain that have yet to be discovered. Though both articles touch on the fact that these discoveries may lead to treatments involving microglia, an actual therapeutic use of these structures has yet to be created. We can be hopeful, however, that as we learn more and more about these defenders of the brain, a treatment for many disorders involving microglia may be just on the horizon.

The Use of TMS in Neurological Research

In Dr. Lawrence Behmer’s work, he uses transcranial magnetic stimulation (TMS) to measure activation of actions in a sequence using a typing task, in order to determine if there was evidence for parallel action regulation in humans. The researchers used strings of words and random strings mainly consisting of letters traditionally typed by the right index finger, and the typists were instructed to relay these strings of words/letters back. Transcranial magnetic stimulation was activated with the first stroke of the key. All of the participants were strongly right-handed. The results showed that there was a main effect for string type, indicating that it was easier for the participants to relay back the words rather than the random strings. There was also a cross interaction between string type and serial position.

Transcranial magnetic stimulation can be used for a variety of different psychological and neurological studies, not only in action regulation as demonstrated above. For example, in Basil et. al. 2005, the researchers reviewed how transcranial magnetic stimulation was used to test whether or not it was an efficient treatment for major depressive disorder in patients who had previously not responded to tradition effective treatments. In several of the studies included, rTMS was proven successful in significantly reducing depression in patients, however, in studies that used other forms, such as HF-rTMS in speeding up or strengthening the therapeutic response to sertraline in major depression, it was shown to have no benefit. This could potentially suggest that rTMS was a superior method as compared to alternative TMS measures.

The research on transcranial magnetic stimulation and its various effects within the body is extensive, yet there are many potential directions future researchers could take its uses. Dr. Behmer has increased its usefulness in his research regarding action regulation, and the researchers in Dr. Basil’s study have indicated that TMS can be useful in a multitude of psychological areas, such as major depressive disorder, obsessive compulsive disorder, and more. The results from these experiments involving TMS show that this form of treatment is useful for several areas of study, and could be the key to many different aspects of psychology and neuroscience going forward.

Resources
Basil, B., Mahmud, J., Matthews, M., Rodriguez, C., & Adetunji, B. (2005). Is There Evidence for Effectiveness of Transcranial Magnetic Stimulation in the Treatment of Psychiatric Disorders? Psychiatry, MMC, 2(11), 64-69.