The Importance of ADHD Research for Adults and Children

 

The article “The Marketing of Stimulants for Children With A.D.H.D.” in the New York Times, by Perri Klass, M.D., discusses the ins and outs of diagnosing and treating ADHD along with the implications of this journey on children, their parents, doctors and society at large. The article highlights the growing number of those being diagnosed and the significance of what age patients are being diagnosed. One major treatment for ADHD includes the prescription of a stimulant. Klass writes “Although medication should be neither the first nor the only treatment used, some children find that the stimulants significantly change their educational experiences, and their lives, for the better”. There is a large debate on whether ADHD medication should be prescribed to children or not, one of the reasons for the ladder includes possible addiction to a substance later in life, which researchers have seen a rise of Adderall misuse/abuse. Klass’ article also encourages one to factor in how the pharmaceutical companies push medications through doctors and the difficulty for parents to know if their child is being prescribed medication for the right reasons. For both children and adult patients getting this diagnosis and knowing what the best treatment can be difficult.

 Continuation of research on ADHD is important because it will be able to give insight on understanding how one is affected by it and the best ways to treat it. In the study “Top-down attention modulates auditory-evoked neural responses in neurotypical, but not ADHD, young adults” Kwasa et al investigates the deficits held by people with ADHD in comparison to those without it. The study focused on 55 young adults, 20 being neurotypical and 25 with ADHD. Kwasa et al assessed the ability of subjects to maintain attentional focus using a sound test, the researchers used an EEG to measure event related potentials (ERPS) specifically looking at N1 and P3 responses. The results of this test showed “attentional modulation was weaker in ADHD listeners, even though their behavioral performance was no lower” (Kwasa et al). The results of the neural responses recorded show that it is more difficult for those with ADHD to keep their attention on a single subject. This applies to and gives evidence for the daily struggle that many people go through having ADHD, for many staying focused at school or work is much more difficult for someone without ADHD.

 For many adults and children their success at school/work is highly affected by their ADHD and therefore they seek treatment. For many this treatment will be the prescription of a stimulant. As mentioned before there is the potential for abuse of such stimulants and that is one reason, I think Kwasa’s study is important. With the found information doctors can have a better sense of how to diagnose future patients and make sure they are prescribing a drug safely. Kwasa et al write, “our results support the idea that behavioral assessments are less sensitive than neural measures of ADHD”. This shows that maybe there needs to be a change in how doctors diagnose. Continuing research similar to this study will improve the treatment for those with ADHD as well as potentially reduce the amount of people that get addicted to the stimulants by wrongly being prescribed. New research based evidence would hopefully also aid in stopping the pharmaceutical companies pushing their prescriptions for wrongful reasons, which increases patient safety and lowering patient’s cost for treatment.

Resources

Klass, Perri, MD. “The Marketing of Stimulants for Children With A.D.H.D.” The New York Times, 10 Feb. 2020, www.nytimes.com/2020/02/10/well/family/the-marketing-of-stimulants-for-children-with-adhd.html?searchResultPosition=1.

Kwasa, Jasmine, et al. “Top-down Attention Modulates Neural Responses in Neurotypical, but Not ADHD, Young Adults.” The Journal of the Acoustical Society of America, vol. 150, no. 4, 2021, p. A64. Crossref, https://doi.org/10.1121/10.0007633.

 

Multiple sclerosis information

 Dr Chen, discussed the neurobiology of M.s and its mechanics. She discussed that MS is the auto immune inflammatory response to the myelin antigens. And that MS, represents activity in the central nervous system (CNS) . And she also talked a little bit about how MS affects the patient, not only physically but biologically as well. As we know many MS patients it isn't something that constantly affects the patient, but similar to many autoimmune diseases there are phases of remission, and disease known as flare ups. When MS flares up the central nervous system is directly affected, the patient experiences increased fatigue of the arms and legs in some severe cases manifestations can include optic neuritis. And other manifestations can include inflammation in the colon IBD. And lupus. Unlike these other autoimmune diseases, MS causes demyelination and loss of oligodendrocytes as discussed by Dr Chen in her talk.

Relapses are fundamentally a manifestation of an inflammatory response occurring mostly in the white matter of the nervous system but also within myelin tracts in the gray matter. This results in focal demyelination with relative axonal sparing. This would account for the development of optic neuritis. Which affects the sight, this explains blurred vision and loss of vision for the patient. The best evidence for inflammation-induced relapses is confirmed through diagnostic imaging; the most reliable diagnostic we can use when dealing with MS would be MRI. which demonstrates the association of relapses with gadolinium enhancement, so a dye is injected intravenously which is disruption of the blood brain barrier. The main pathologic hallmark of MS is the demyelinated plaque, which has specific histological and immunohistological characteristics depending on the activity of the disease. This is the main indicator to diagnose MS. There have been cases of MS and inflammation causing lesions which are benign. This is most common, in the early phases of the diesease. To diagnose MS, the other diagnostic test used aside from imaging would be simple blood work. The stress induced blood marker that helps indicate MS induced stress kinases is elf2a. This is produced through a simple lab

Multiple sclerosis

 Dr Chen, discussed the neurobiology of M.s and its mechanics. She discussed that MS is the auto immune inflammatory response to the myelin antigens. And that MS, represents activity in the central nervous system (CNS) . And she also talked a little bit about how MS affects the patient, not only physically but biologically as well. As we know many MS patients it isn't something that constantly affects the patient, but similar to many autoimmune diseases there are phases of remission, and disease known as flare ups. When MS flares up the central nervous system is directly affected,  the patient experiences increased fatigue of the arms and legs in some severe cases manifestations can include optic neuritis. And other manifestations can include inflammation in the colon IBD. And lupus. Unlike these other autoimmune diseases, MS causes demyelination and loss of oligodendrocytes as discussed by Dr Chen in her talk.  Relapses are fundamentally a manifestation of an inflammatory response occurring mostly in the white matter of the nervous system but also within myelin tracts in the gray matter. This results in focal demyelination with relative axonal sparing. This would account for the development of optic neuritis. Which affects the sight, this explains blurred vision and loss of vision for the patient. The best evidence for inflammation-induced relapses is confirmed through diagnostic imaging; the most reliable diagnostic we can use when dealing with MS would be MRI. which demonstrates the association of relapses with gadolinium enhancement, so a dye is injected intravenously which is disruption of the blood brain barrier. The main pathologic hallmark of MS is the demyelinated plaque, which has specific histological and immunohistological characteristics depending on the activity of the disease. This is the main indicator to diagnose MS. There have been cases of MS and inflammation causing lesions which are benign. This is most common, in the early phases of the diesease. To diagnose MS, the other diagnostic test used aside from imaging would be simple blood work. The stress induced blood marker that helps indicate MS induced stress kinases is elf2a. This is produced through a simple lab. 

Research in Ms

Dr Chen, discussed the neurobiology of M.s and its mechanics. She discussed that MS is the auto immune inflammatory response to the myelin antigens. And that MS, represents activity in the central nervous system (CNS) . And she also talked a little bit about how MS affects the patient, not only physically but biologically as well. As we know many MS patients it isn't something that constantly affects the patient, but similar to many autoimmune diseases there are phases of remission, and disease known as flare ups. When MS flares up the central nervous system is directly affected,  the patient experiences increased fatigue of the arms and legs in some severe cases manifestations can include optic neuritis. And other manifestations can include inflammation in the colon IBD. And lupus. Unlike these other autoimmune diseases, MS causes demyelination and loss of oligodendrocytes as discussed by Dr Chen in her talk.  Relapses are fundamentally a manifestation of an inflammatory response occurring mostly in the white matter of the nervous system but also within myelin tracts in the gray matter. This results in focal demyelination with relative axonal sparing. This would account for the development of optic neuritis. Which affects the sight, this explains blurred vision and loss of vision for the patient. The best evidence for inflammation-induced relapses is confirmed through diagnostic imaging; the most reliable diagnostic we can use when dealing with MS would be MRI. which demonstrates the association of relapses with gadolinium enhancement, so a dye is injected intravenously which is disruption of the blood brain barrier. The main pathologic hallmark of MS is the demyelinated plaque, which has specific histological and immunohistological characteristics depending on the activity of the disease. This is the main indicator to diagnose MS. There have been cases of MS and inflammation causing lesions which are benign. This is most common, in the early phases of the diesease. To diagnose MS, the other diagnostic test used aside from imaging would be simple blood work. The stress induced blood marker that helps indicate MS induced stress kinases is elf2a. This is produced through a simple lab.

What if one day, you couldn’t remember anymore?

What if one day, you couldn’t remember anymore? Memories of family, life, love, identity, and education- all becoming more and more unfamiliar. The abilities to learn and remember are aspects of life that are utilized every single day, but are often taken for granted. In the United States, 1 in 9 people age 65 and older has Alzheimer’s dementia1. Alzheimer’s disease is a form of dementia that is characterized by neurodegeneration of the hippocampus, resulting in decline of memory, thinking, and reasoning skills. 

In order to determine what mechanisms are responsible for synapse degradation in the hippocampus, identification of the neural components that strengthen a synapse are crucial to proposing a treatment method. Long term potentiation is a form of synaptic plasticity that results in the strengthening of a synapse by an increase of postsynaptic density 95 (PSD95), which stabilizes synaptic changes in long term potentiation by increasing NMDA/AMPA receptors of excitatory synapses. Increases in PSD95 also result in dendritic spine growth, thus strengthening the excitatory synapse. In an individual with Alzheimer’s, hippocampal excitatory neurons undergo long term depression (LTD) by excessively decreasing PSD95, thus resulting in a weakened synapse. 

In the article, “Pin1 Binding to Phosphorylated PSD-95 Regulates the Number of Functional Excitatory Synapses”, Delgado et. al investigate the mechanisms responsible for the regulation of PSD-95 at synapses, and what implications such mechanisms may have on potential treatments for neurodegenerative diseases. Pin1 is an enzyme that is known for its involvement in diseases such as Alzheimer’s, leading to investigation of its involvement with PSD-95. Delgado et. al exhibit that phosphorylation of PSD95 allows Pin1 to bind and cause long term depression by decreasing dendritic PSD95 and number of functional excitatory synapses. Additionally, knocking out Pin1 showed an increase in size and number of post synaptic spines, which could imply a potential treatment for degenerative diseases such as Alzheimer’s.

It is important to note that Pin1 plays a role in multiple aspects of cellular functioning- particularly cell cycle regulation and survival. In “Inverse Correlation between Alzheimer’s Disease and Cancer”, Zablocka explains that Pin1 KO mice showed a resistance to cancer, however they displayed neurodegenerative Alzheimer's-like symptoms. This finding suggests that Pin1 has a crucial regulatory mechanism. Zablocka details that Pin1 is responsible for maintaining a trans-conformation of tau and APP neuronal proteins, which promote functional neuron activity. A cis-conformation of APP results in an increase of B-Amyloid, which is characteristic of Alzheimer’s dementia. Inducing overexpression of Pin1 in the KO mice resulted in a decreased level of B-Amyloid; thus concluding that Pin1 plays a significant role in neuronal regulatory mechanisms- despite its influence on PSD. The increase in number of synaptic spines as a result of Pin1 inhibition could be a result of lack of regulatory mechanisms within the neuron- not necessarily beneficial to the strengthening of synapses. 

Pin1’s role in LTD and LTP can be considered for treatment and regulation of neurodegeneration, given its implications on conformational changes which influence B-Amyloid; however, more detailed signaling cascades such as Pin1’s influence on Wnt signaling and beta-catenins can be further investigated to further target the mechanisms of neurodegeneration and LTP.

References:

https://link.springer.com/article/10.1007/s12035-021-02544-1

https://www.frontiersin.org/articles/10.3389/fnmol.2020.00010/full 

The Future of Spinal Cord Injury Rehabilitation

 The approach to researching spinal cord injuries and their treatments are way different than treatments in other tissues where cells have the ability to repair. After a spinal cord injury, axons of neurons become severed/demyelinated. There is little to no recovery of nervous tissue function and tissue degeneration is progressive. It is not that the neuron is incapable of neuroplasticity, rather it is prevented by its environment because the immune system initiates scar tissue formation around the contusion as a barrier to contain the injury. This makes it hard for axons to regenerate and communicate with each other. Li et al. used a nanofiber-hydrogel composite (NHC) to modulate inflammation after spinal cord injury in rodents. The article “‘Dancing Molecules’ Successfully Repair Severe Spinal Cord Injuries” by Northwestern discusses recent research conducted by Alvarez et al. These researchers have engineered an injectable therapy using nanofibers in rodent models similar to Li et al. It is a supramolecular peptide fibril scaffold that includes two peptide sequences: one sequence focuses on inflammation and scarring whereas the other sequence promotes blood vessel formation. This therapy mimics the natural environment around the spinal cord where the molecules within the nanofibers move or “dance” out of the supramolecular polymers to engage with cell receptors. Morris states “This is the first study in which researchers controlled the collective motion of molecules through changes in chemical structure to increase a therapeutic’s efficacy” (Northwestern). Alvarez et al. hypothesized that if the molecules are dancing around, the probability that the molecules will meet up with the receptors is increased. They found that the more the molecules moved, the more successful the therapy was in recovering function in the mouse whose lower body was paralyzed. After a single injection into the rodent spinal cord, the animal was able to walk after four weeks. Many implications can be inferred from this research. The life expectancy and quality of life of spinal cord injury patients would be increased. However, the most important implication is that the supramolecular motion studied by Alvarez et al. can not only be applied to spinal cord injury therapy, but also other therapies as well.

Works Cited

Morris, Amanda | By Amanda Morris. 'Dancing Molecules' Successfully Repair Severe Spinal Cord Injuries, 11 Nov. 2021, https://news.northwestern.edu/stories/2021/11/dancing-molecules-successfully-repair-severe-spinal-cord-injuries/. 

A Baby’s Circadian Rhythm

             All humans have very similar circadian rhythms, and we can adjust it based on our everyday lives. Most everyone’s circadian rhythms are to wake up in the daytime and sleep at night. Some sleep later than others and some earlier. If you work at night your circadian rhythm is different as you sleep in the daytime and is awake at night. Adolescences and teenagers have similar circadian rhythms as they got to wake up early to go to school for 8 hours and then study and then back to bed to wake up early again. But what about babies? Babies are unpredictable as they can sleep all day and cry all night or vice versa on a good day. But one’s thing for sure is that babies need plenty of rest. But how do they know that they need it?

            The fruit fly or the Drosophila melanogaster is one species that is studied the most when it comes to circadian rhythms due to their many different behavior outputs. The molecular clocks in the brain and fat body of control flies gradually grow out of phase with one another under free-running conditions (Fulgham et al., 2021). This can be seen in humans as well as babies grow out of their unique molecular clocks and start to mold their new clocks into what society has created for humans growing up.

            Sleep and development go hand in hand when it comes to babies and them growing. In fruit flies, the period of feeding rhythms tracks with molecular oscillations in central brain clocks cells, consistent with a primary role of the brain clock in dictating the time of feeding behavior (Fulgham et al., 2021).  This is the same with babies in which they have responsive feeding, which means responding to a baby’s hunger cues, rather than feeding on a set schedule (Ruggeri, 2022). 

 

References

Fulgham, C. V., Dreyer, A. P., Nasseri, A., Miller, A. N., Love, J., Martin, M. M., Jabr, D. A.,     Saurabh, S., & Cavanaugh, D. J. (2021). Central and Peripheral Clock Control of         Circadian Feeding Rhythms. Journal of Biological Rhythms, 36(6), 548-566.             https://doi:10.1177/07487304211045835

Ruggeri, A. (2022, February 8). The Science of Healthy Baby Sleep. BBC Future. Retrieved        March 4, 2022, from 

            https://www.bbc.com/future/article/20220131-the-science-of-safe-and-healthy-baby-sleep

Circadian Rhythm Disruption and Alzheimer’s Disease

There are many different behavioral patterns of organisms that are under the control of 24-hour light-dark cycles called circadian rhythms. These circadian systems are responsible for biological and physiological outputs such as feeding behavior, sleeping, as well as hormone release and regulation. However, the genetic circuitry underlying circadian rhythms can easily be disrupted by factors such as light-noise, jet-lag, blue light, and a variety of other factors (Sharma et al., 2021). Circadian rhythm disruptions are shown to be detrimental to both behavioral output and cognitive function. 

Circadian systems play a large role in hippocampal memory formation, which is influenced by the GABA hormone released from the suprachiasmatic nucleus (SCN) (Ruby et al., 2008). In the article, “Circadian Rhythm Disruption and Alzheimer’s Disease: The Dynamics of a Vicious Cycle.”, Sharma et al. investigate how circadian rhythm disruptions contribute to Alzheimer’s disease (AD). Alzheimer’s is characterized by a loss of memory and cognitive function, with postmortem analysis of AD brains revealing desynchronized central circadian clock expression and disrupted hormone cycles (Cermakian et al., 2011). Transgenic mice mimicking the circadian rhythm disruption of jet-lag exhibited significant memory impairment and hippocampal neurogenesis compared to the memory performance of control mice. Furthermore, realignment of disrupted circadian systems were found to improve some of the cognitive symptoms exhibited in patients with advanced AD (Sharma et al., 2021). This study indicates that the pathology of AD is supported and reinforced by disruptions to the genetic mechanisms underlying circadian rhythms.          

A similar study titled “Central and Peripheral Clock Control of Circadian Feeding Rhythms” by Fulgham et al. explores the effect of molecular circadian clock manipulations on the feeding behavior of fruit flies, or Drosophila melanogaster. The researchers determined that the molecular clocks in both brain and peripheral tissues are largely responsible for feeding rhythms. Central brain clocks were found to dictate the ultimate timing of feeding rhythms, unlike the fat body clocks in peripheral tissue. When the molecular clocks in multiple peripheral cells were disrupted, fruit flies consumed less and had a reduced feeding rhythm strength (Fulgham et al., 2021). Ultimately, this study demonstrates how disruptions to circadian rhythms can be detrimental to important biological processes such as food intake.

Both studies reveal the importance of circadian rhythms and how they can greatly influence the overall health of an organism. While some believe exchanging sleep for another activity may be beneficial, it will ultimately have greater long-term impacts. Circadian rhythm disruptions can have extreme adverse biological and physiological effects, indicating how critical it is to have healthy sleep habits. It is the active implementation of these habits that can potentially realign disrupted circadian rhythms and help improve overall quality of life.   

                           

References

Cermakian, Nicolas et al. “Circadian clock gene expression in brain regions of Alzheimer 's disease patients and control subjects.” Journal of biological rhythms vol. 26,2 (2011): 160-70. doi:10.1177/0748730410395732

Fulgham, C.V., Cavanaugh, D.J., et al. “Central and Peripheral Clock Control of Circadian Feeding Rhythms.” Journal of Biological Rhythms, vol. 36, no. 6, SAGE Publications, 2021, pp. 548–566., https://doi.org/10.1177/07487304211045835.

Ruby, N.F. et al. “Hippocampal-dependent learning requires a functional circadian system.” Proceedings of the National Academy of Sciences of the United States of America vol. 105,40 (2008): 15593-8. doi:10.1073/pnas.0808259105

Sharma, Ashish, et al. “Circadian Rhythm Disruption and Alzheimer’s Disease: The Dynamics of a Vicious Cycle.” Current neuropharmacology 19, no. 2 (2021): 248–264., https://doi.org/10.2174/1570159X18666200429013041.

Further Speculation of the Circadian Rhythmic Effects on Food Addictions, and More

     With obesity being declared an ongoing and growing pandemic in the 21st century, researchers have been showing high interest in the biological role of our bodies which either induce, or prevent cases of obesity. As such, it has been highly beneficial to find linkage between different circadian rhythmic loops, and their effect on the body's metabolic rate. This is why the article Central and Peripheral Clock Control of Circadian Feeding Rhythms, by Carson V. Fulgham et al., is an excellent foundational study for the implications circadian feeding loops have on our feeding patterns, and on health in general.

    The experiment performed by Fulgham and his team studied multiple circadian timing systems found in the fruit fly, or drosophilia melanogaster, specifically focusing on clock cells which included a circadian clock for feeding rhythms. The article explained the mechanisms of these clock cells, stating that they functioned by the oscillations in gene expression underwent during the ~24 hour periods considered the length our "biological clocks". The specific genes activated were core clock genes period (per) and timeless (tim), which were dependent on transcriptional activators CLOCK (CLK) and CYCLE (CYC) to be transcribed. The proteins are synthesized, then sent back into the cell to repress their transcriptional-driving factors CLK and CYC, marking the end of the cycle. In the study, the research team manipulated this organic system in two ways; (1) By integrating GAL4 transcription factors into the circuit to shift the phase of the feeding rhythm, and (2) by perpetuating complete hindrance of the clock cell tissues by introducing CRISPR-Cas9 to the flies' systems in order to eliminate the production of per and tim, ultimately restricting the entire function of the clock systems. Furthermore, they tested several different clock cell tissues, including brain circuits, peripheral tissue, and the fat body of Drosophilia, which mimic adipose tissue in mammals by secreting factors, such as leptin, which are directed to the hypothalamus (where the brain clock cells are mediated), ultimately inhibiting feeding.  Each tissue sample was tested in order to determine what role each of them play in the feeding rhythms, if any. 

    The findings revealed that the circuits in the brain heavily dictated the periods, and overall occurrence, of feeding rhythms. This conclusion came about because it was found that altering the cells with dbt would slow the feeding rhythm oscillations in the brain, and sgg would speed up the oscillations. However, when the peripheral tissue and that of the fat body was tested, it showed no output on the feeding rhythms. Then again when the central brain clock was completely knocked out, arhythmic patterns emerged in the flies' feeding once again. 

    The implications you can draw from the conclusions of Fulgham's study are that not only are our circadian rhythm systems accountable for feeding patterns, but they are not indefinite, and can be altered, much to our benefit, as we know that we our circadian rhythm also controls events such as our metabolic activity levels, and insulin sensitivity. Therefore, it is important for us to optimize our feeding patterns so that they are in line with our bodily circadian mechanisms.

    The article The Effects of Individual Circadian Rhythm Differences on Insomnia, Impulsivity, and Food Addiction, by Ali Kandeger et al., addresses the slight changes that can occur in our circadian rhythms, based on environmental stimuli, and how those implicitly effect food addiction, and obesity. The team conducts a study on college students who show behaviors of either morning type, neither type, or evening-type circadian rhythms. The paper includes connections between evening-type individuals having a slower oscillation period than morning type individuals, as well as habits such as insomnia, which leads to sleep deprivation, which is known to cause an increase in appetite and food-intake. Other habits include late-night cravings, and skipping meals, which are characteristics of individuals who are prone to developing high cholesterol, diabetes, and becoming obese. From all the previous recorded evidence, Kandeger and her team hypothesized that participants who showed evening-type circadian rhythm patterns would have indirectly developed an increase in food addiction because of a direct development of insomnia and sleep deprivation. 

    After performing a cross-sectional study to analyze the correlation between circadian rhythmic differences and food addiction, it was concluded there was no significant correlation between food addiction and circadian preference. However, because there was a correlation between evening-type people and insomnia/ sleep deprivation, there still exists an indirect linkage between evening-type circadian rhythms and food addiction, ultimately leading to obesity and many other health problems.

    While it was discovered that our circadian clocks are not directly responsible for our habits or addictions, both studies concluded how they have a major impact on the way we process food metabolically, as well as attributes on other habits and disorders which opens the door to a web of future health problems, one of which being obesity. The studies also included scientific evidence that our internal clocks can be adjusted, whether that is via environmental stimuli, or by chemical intervention. Further studies to determine how we can optimize our circadian rhythm patterns could potentially benefit human health in many regards, such as by lowering susceptibility for obesity. Hence, both of these foundational and contemporary studies are a great starting point for the science on this topic to advance in the near future.

References

Fulgham, Carson V., et al. “Central and Peripheral Clock Control of Circadian Feeding Rhythms.” Journal of Biological Rhythms, vol. 36, no. 6, 2021, pp. 548–566., https://doi.org/10.1177/07487304211045835.

Kandeger, Ali, et al. “The Effects of Individual Circadian Rhythm Differences on Insomnia, Impulsivity, and Food Addiction.” Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, vol. 24, no. 1, 2018, pp. 47–55., https://doi.org/10.1007/s40519-018-0518-x.

Girls with ADHD - Not So Different

 

        In her paper, Top-down Attention Modulates Auditory-evoked Neural Responses in Neurotypical, but not ADHD, Young Adults, Jasmine A.C. Kwasa Ph.D. measures both behavioral performance and key neural signatures of attention using electroencephalography (EEG) during an especially demanding listening task for ADHD and neurotypicals. Participants were to focus on a target speech sound while choosing to either ignore or engage with other auditory stimuli functioning as 'interrupters' and 'distractors.' Kwasa and her team's findings expectedly show decreased attentional modulation, demonstrated by neural signatures, for ADHD subjects. However, researchers found no difference between groups in terms of behavioral performance - everyone varied behaviorally in how they attended to a target, no clear behavioral difference for ADHD folks (man or woman). This is relevant for when we think of what ADHD symptoms should look like and for who. 

        According to the Center for Disease Control and Prevention (CDC), boys are more than twice as likely to receive an attention-deficit/hyperactivity disorder (ADHD) diagnosis - 12.9% boys to 5.6% girls. Rae Jacobson from the Child Mind Institute cites co-founder and director of the National Resource Center for Girls and Women with ADHD, Patricia Quinn, MD, and Clinical Psychologist, Stephen Hinshaw, Ph.D., and Clinical Psychologist, Kathleen Nadeau Ph.D. in her article, How Girls With ADHD Are Different. Best put by Dr. Nadeau, “Girls are under a lot more pressure to be socially tuned in and self-controlled.” Dr. Quinn describes an image of little boys with ADHD bouncing off walls, known and accepted well in our hegemonic society. However, when children begin to grapple with their ADHD symptoms, frustrations are natural. What differs is the socially acceptable way of expressing those frustrations. Boys are allowed and expected to do so externally while girls are confined to express their frustrations internally. This can manifest as low self-esteem, lack of self-advocacy in the classroom, and severe impacts on mental health. Dr. Hinshaw's own research finds that girls with ADHD have significantly higher rates of attempted suicide and self-harm than girls without.  

It appears as though, in the controlled environment of the lab, the complex influences of gender roles in our society seem to fall away. It begets the question, that if women and girls were not so constrained to the performance of their gender, would their ADHD symptoms look more like that of boys? Now the fact that behavioral indicators of attention continue to prove non-distinctive between neurotypicals and folks with ADHD, might not make accurately diagnosing girls easier, but it is important science that propels us towards a more equal society. 

“Data and Statistics about ADHD.” Centers for Disease Control and Prevention, U.S. Department of Health & Human Services, 23 Sept. 2021, https://www.cdc.gov/ncbddd/adhd/data.html.

Jacobson, Rae. “How Girls with ADHD Are Different.” Child Mind Institute, 15 Feb. 2022, https://childmind.org/article/how-girls-with-adhd-are-different/.

Spinal Cord Injuries Treatments

 

As we know the brain and spinal cord are the two regions of the body that are associated with the central nervous system. In other words, damage to any of these regions would lead to the loss of proper functioning of the body. The progressive loss of neurons/axons is typically referred to as neurodegeneration, the hallmark of CNS injury. Damage to the CNS can cause an onset of diseases such as Alzheimer's, PLS, ALS, MS, and much more. A famous actor by the name of Christopher Reeves played the DC superhero, superman, during the 1980s. Superman, also known as the man of steel, is an indestructible alien but sadly Reeves is just a human. On May 27, 1995, the actor injured his spinal cord after falling off his horse in an equestrian competition. He landed directly on his head where he broke two vertebrae in his neck. Luckily, his spinal cord was not completely damaged, however, there was a large hemorrhage at the site of the injury. Reeves was paralyzed from the waist down and was mandated to be attached to a mechanical ventilator in order for him to survive. He lost his entire career and almost his life. This story further exemplifies the detrimental effects associated with damaged regions regarding the CNS. Many researchers today are finding various methods in neural tissue repair and regeneration in order for people to have proper functioning of their body. Sadly, we do not have the proper amount of research or information on the spinal cord to treat these damaged areas. 

 A 2020 study by Dr. Oudega takes a look at the effects of a nanofiber-hydrogel composite (NHC) on neural tissue repair on the spinal cord and whether this method can be used to treat any kind of spinal cord injury in humans. The researchers in this study used a rat as the model organism and through the injection of NHC, it provided mechanical support and a microenvironment to the contused spinal cord which plays an important role in nervous tissue damage and repair. A spinal cord contusion leads to a loss of nervous tissue thus the body is unable to elicit any repair/regeneration (Li et al. 2020). Furthermore, without any exogenous factors, NHC supported angiogenesis, axonal growth, neurogenesis at the injured site, and pro-regenerative macrophage polarization. It can be seen that these researchers developed a method for repairing damaged nervous tissue within spinal cord contusions (Li et al. 2020). However, it is important to note that these positive effects were only seen in rats and human trials haven’t been conducted yet. It can be seen that we are one step closer to neural regeneration which could help many people that are suffering from diseases associated with spinal cord injuries. 

 A recent 2020 news article takes a look at a different approach in neurotypical regeneration via a stem cell treatment after the spinal cord injury. Mayo Clinic is conducting human clinical trials of stem cell treatment with individuals suffering from severe spinal cord injury. This clinical treatment is called CELLTOP which involves injections of autologous adipose-derived stem cells into the spinal cord (Windebank 2020). It can be seen that a patient who underwent phase 1 of this procedure showed a dramatic improvement in the functioning of his upper and lower extremities. Sadly, not all patients responded in the same way, some showed dramatic improvement others not so much (Windebank 2020). However, it is important to note that the effects of this treatment plateaued after six months, therefore, the patient was reinjected which led to a significant improvement in grip strength and his overall range of motion.

Through both studies, it can be seen that we have made a significant improvement in regaining the physiological function of the body's extremities associated with neurotypical damage to the spinal cord. Much research still has to be done but we are one step closer to curing people with lifelong spinal cord damage. 

 References 

Li, X., Zhang, C., Haggerty, A. E., Yan, J., Lan, M., Seu, M., Yang, M., Marlow, M. M., Maldonado-Lasunción, I., Cho, B., Zhou, Z., Chen, L., Martin, R., Nitobe, Y., Yamane, K., You, H., Reddy, S., Quan, D. P., Oudega, M., & Mao, H. Q. (2020). The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord. Biomaterials, 245, 119978. https://doi.org/10.1016/j.biomaterials.2020.119978 “Neurology and Neurosurgery.” Mayo Clinic. Mayo Foundation for Medical Education and Research. Accessed March 4, 2022. https://www.mayoclinic.org/medical-professionals/neurology-neurosurgery/news/stem-cell-treatment-after-spinal-cord-injury-the-next-steps/mac-20488605.

Attentional Deficit in Individuals with ADHD Is Modality-Specific

Attention-deficit/hyperactivity disorder or ADHD is a neurodevelopmental disorder characterized by a pattern of hyperactivity, impulsivity, and attention deficits in different sensory modalities. In particular, many studies have been done to understand attention deficits associated with ADHD by contrasting attentional performance between individuals with and without ADHD. For example, “Top-down attention modulates auditory-evoked neural responses in neurotypical, but not ADHD, young adults” provides insight into auditory attention deficits in individuals with ADHD by comparing top-down attentional control in young adults with and without ADHD (Kwasa et al. 2021); Dr. Kwasa and colleagues looked at differences in both behavior as well as neural responses measured by electroencephalogram (EEG), while both groups of subjects completed auditory selective attention tasks. Specifically, they looked at N1 and P3 event-related potentials in EEG to determine how each individual’s top-down attention and bottom-up attention modulate in response to different auditory stimuli, respectively. The auditory tasks required participants to pay attention only to target syllables and ignore interrupters (FOCAL trials), or to pay attention to target syllables and interrupters as they show up (BROAD trials). Overall, they found that performance was significantly better in the FOCAL trials than in BROAD in both groups, as subjects did not have to anticipate potential distractions. They also found that attention modulated N1 more weakly in ADHD subjects than did subjects without ADHD, suggesting weaker top-down control attention in ADHD subjects. Finally, individual differences in top-down control of attention directly relate to differences in performance, but ADHD status did not have a significant effect on performance. 

As sensory information overlaps with different modalities, it is fair to assume that the degree of attention deficit in each modality within an individual should be correlated as well. However, little is known about the interaction between attention deficits in different sensory modalities prior to the paper “Relationship between intraindividual auditory and visual attention in children with ADHD” (Lin et al. 2021). In this paper, Lin and colleagues examined two dimensions of attention, vision and sound, in children with and without ADHD. Each participant underwent two tests of variables of attention (visual version and auditory version), from which anticipatory responses (ANTI) were calculated and a higher number indicated greater deficit. Overall, they found a higher ANTI on the vision version than the auditory version in subjects with ADHD compared to controls, suggesting that visual attention is more impaired than auditory attention in the ADHD group. Most importantly, when they looked at ANTI within each ADHD subject, they found little correlation between vision and auditory attention, indicating that the mechanism of attentional deficits in individuals with ADHD is modality-specific; In other words, one could have visual attentional deficits (high ANTI) and not auditory attentional deficits (low ANTI), and vice versa.

Together, these two papers are important as they deepen our understanding of attention deficit in individuals with and without ADHD by highlighting its manifestation in one specific modality and the (lack of) relationship between two different modalities, respectively: Kwasa et al. specifically investigated the role of top-down control in modulating auditory attention in adults, whereas Lin et al’s study discovered separate mechanisms of visual and auditory attention deficits in children. A future experiment combining results from these two studies could look at how top-down attentional control modulates both modalities simultaneously in children with ADHD. 

References

Kwasa, Jasmine A. C. et al. “Top-down attention modulates auditory-evoked neural responses in neurotypical, but not ADHD, young adults.” bioRxiv (2021): n. Pag.

Lin, Hung-Yu, et al. "Relationship between intraindividual auditory and visual attention in children with ADHD." Research in Developmental Disabilities 108 (2021): 103808.

Microengineered hydrogel cell therapies for Spinal Cord regeneration

 It is quite obvious that an injury to the spinal cord  is never good news. Usually, any damage to the spinal cord fails to completely heal (though may progress overtime) because nerve cells are not able to regenerate. Injury may cause scarring to the area of the spinal cord, not allowing nerve cells the space/adequate surface area needed in order to be able to regenerate affected nerve fibers which are sometimes trapped within the scar tissue. Unfortunately, if an individual suffers from a spinal cord injury (dependent of the location on the spinal cord) they may have a variety of diseases develop due to the harm done to the nerves of the spinal cord. A few of these diseases  may include tumors, infections like meningitis and polio, autoimmune disease, and degenerative diseases such as spinal muscular atrophy. Paralysis may also concede and can be a whole body (medically coined as tetraplegia/quadriplegia) paralysis or a paralysis which only affects the lower body (paraplegia). 

Now, why is research on treatments for spinal cord injury so relevant and not to be taken lightly? Well “Why is the spinal cord important?”  -this is a question which can be entered  into google search with results yielding something along the lines of the spinal cord helps the brain send nerve signals to the entire body; and inversely, the spinal cord helps the body send nerve signals to the brain. Why is THIS important? Well, the brain must be able to control the physical body based on wants and needs which are dictated by the physical interactions the the body may be experiencing. So, since the brain is the commander, the spinal cord is something along the lines of a messenger for the physical body and its movements of function. 

At Loyola University Chicago where I attend as a major in Biology, I have also picked up a minor in neuroscience, (Siri, what is neuroscience? The study of how the nervous system develops— it has a focus on the brain and its impact on  behavior and cognitive function.) here, I had the pleasure and complete privilege of being able to attend a neuroscience based seminar where therein I am able to listen to research conducted by fascinating professionals in STEM and the contextual neuroscience field. This last week in February, I was able to attend a research presentation introduced by Dr.Martin Oudega, a research scientist and Professor currently at Northwestern University in Illinois.

 During the seminar, the study “The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord” was introduced, explained, and discussed. For context, in this experiment, the hydrogel used was made from hyaluronic acid or HA (which is a  substance naturally produced by and found in the body—skin, connective tissue and eyes).  As stated  above, spinal cord injuries cause loss of nerve tissues because of limited ability of fiber regeneration at the site due to scarring. Dr.Martin Oudega explains how an injectable nano fiber-hydrogel was engineered and how this hydrogel was injected into 15 rat specimen which were anesthetized first and then contused and with  spinal cords left exposed. Over the course of the  experiment, it was found that the NHC or nanofiber-hydrogel composite was successful in providing mechanical support to the contusion on the spinal cord and enhanced pro-regenerative macrophage polarization, angiogenesis, axon growth, and neurogenesis in injured nerve tissue.

Similarly, there is a recent cell therapy study published using induced pluripotent stem cell-derived neurons as an approach for spinal cord injury regeneration. This study was published February 07, 2022 and is titled “Regenerating the Injured Spinal Cord at the Chronic Phase by Engineered IPSCs-Derived 3D Neuronal Networks” by Lior Wertheim,Reuven Edri,Yona Goldshmit,Tomer Kagan,Nadav Noor,Angela Ruban,Assaf Shapira,Irit Gat-Viks,Yaniv Assaf,Tal Dvir.

In this study, somatic cells from the patient are used and “re-programmed” in order to be differentiated to the desired cells. These cells are injected to the injury site as well as pre-formed 3D neuronal networks are inserted in place of naturally produced scar tissue.  The idea behind this study was that the insertion of the neuronal network would create an embryonic-like environment  where nerve tissue could actually regenerate in comparison to scar tissue where regeneration  is obviously limited. This study also utilized a hydrogel composite composed of ECM (extracellular matrix- network fo protein/other molecules which surround and give structure to cells/tissue) was used. This hydrogel provided the an inductive microenvironment sufficient to attract progenitor cells  (descendants of stem cells which  further differentiate into specialized cell types of that same tissue).  Alike the Dr.Martin Oudega’s experiment, this study was also positive in its findings. Analysis of cellular content displayed reduced inflammation and elevate expressions of markers associated with growing axons during regeneration were found. Interestingly, this study  suggests that a personalized gel can be cellularly engineered specific to the individual by taking  a small biopsy of somatic cells from the patient. 

Both of these studies are exceedingly interesting. One suggests an approach to spinal cord nerve regeneration by means of a hydrogel which can reprogram cells within an ECM based induced environment specific/personalized to the individual patient. The other study further explores the induction of a hyaluronic acid based nanofiber-hydrogel which can treat spinal cord injury by enhancing/motivating mechanical support to the contused spinal cord area and further producing regenerative growth and genesis of injured tissue without the need for other exogenous factors. 

Both of these studies aid in further positive directions for treatments for those suffering from paralysis and spinal cord injury-rooted diseases.

Li, Xiaowei, et al. “The Effect of a Nanofiber-Hydrogel Composite on Neural Tissue Repair and Regeneration in the Contused Spinal Cord.” Biomaterials, vol. 245, 2020, p. 119978., https://doi.org/10.1016/j.biomaterials.2020.119978. 

Wertheim, Lior, et al. “Regenerating the Injured Spinal Cord at the Chronic Phase by Engineered Ipscs‐Derived 3D Neuronal Networks.” Advanced Science, 2022, p. 2105694., https://doi.org/10.1002/advs.202105694. 

Recent Efforts Toward Regeneration in the Spinal Cord

It is a widely accepted fact in the scientific community that the central nervous system (CNS) is generally incapable of regeneration following an injury. Individuals living with spinal cord injuries (SCIs) and traumatic brain injuries (TBIs) face much lower life expectancies and qualities of life than those without CNS damage. For this reason, one of the most prominent areas of recent neuroscientific research has been determining how to promote regeneration and repair in the brain and spinal cord by exogenous means, to restore complete physical and cognitive function to individuals sustaining injuries of these regions. The two research groups discussed in this entry have independently devised and tested the use and efficacy of different materials in treating SCIs.

In their 2020 research article, "The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord," Dr. Oudega et al. propose an injectable nanofiber-hydrogel composite (NHC) for the promotion of neural repair in the contused spinal cords of adult rats, tested against various other injectable hydrogels and an untreated control group. This research group sought to maximize both the mechanical strength and the porosity of the composite, in order to prevent the injured spinal cord from collapse and to encourage vascularization and axonal growth through the injured region. Their findings demonstrated that NHC better fulfilled these purposes than did simple hydrogels. In addition, the use of NHC was observed to give preference to pro-regenerative M2 macrophages in the injured region over the pro-inflammatory M1 phenotype.

Dr. Álvarez et al. report similarly successful results in their 2021 article, “Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury,” which details the use of injectable supramolecular polymers to which two bioactive signals are attached. One of these signals promotes neural stem cell differentiation and axonal growth, while the other promotes cellular proliferation. This research group tested the efficacy of several materials that varied in polymer composition and signals. It was observed that the most noticeable SCI recoveries occurred in mice treated with a coassembly of polymers which contained both signals and whose chemical structures minimized interactions between molecules and maximized mobility throughout the area. As a result, the regenerative signals associated with these molecules were allowed to interact with nearby cells and foster neurogenesis and angiogenesis in the contused region.

The results of both previously mentioned research groups have yet to be replicated in human subjects with SCIs similar to those of the rodent subjects, as well as being approved for common medical use. However, these findings demonstrate significant progress in the scientific community towards an effective and accessible treatment for SCIs. It would be valuable to determine whether the regenerative effects of the materials used in either experiment would be enhanced if a composite material were produced. Another question of note is whether a material, similar to those that mimicked the extracellular matrix of the spinal cord, could be produced which mimics the functions of glial cells lost to TBIs or neurodegenerative diseases.

 

References:

 

Álvarez, Z., Kolberg-Edelbrock, A. N., Sasselli, I. R., Ortega, J. A., Qiu, R., Syrgiannis, Z., Mirau, P. A., Chen, F., Chin, S. M., Weigand, S., Kiskinis, E., & Stupp, S. I. (2021). Bioactive scaffolds with enhanced supramolecular motion promote recovery from Spinal Cord Injury. American Association for the Advancement of Science, 374(6569), 848–856. https://doi.org/10.1126/science.abh3602

Li, X., Zhang, C., Haggerty, A. E., Yan, J., Lan, M., Seu, M., Yang, M., Marlow, M. M., Maldonado-Lasunción, I., Cho, B., Zhou, Z., Chen, L., Martin, R., Nitobe, Y., Yamane, K., You, H., Reddy, S., Quan, D.-P., Oudega, M., & Mao, H.-Q. (2020). The effect of a nanofiber-hydrogel composite on Neural Tissue Repair and regeneration in the contused spinal cord. Biomaterials, 245, 119978. https://doi.org/10.1016/j.biomaterials.2020.119978

Morris, Amanda. 'Dancing Molecules' Successfully Repair Severe Spinal Cord Injuries, news.northwestern.edu/stories/2021/11/dancing-molecules-successfully-repair-severe-spinal-cord-injuries/.

Circadian Rhythms: Light and Mood

The circadian system is made up of different types of molecular clocks that track behavioral output under hours of the day, typically running under a full 24 hours. In an article about how this system controls feeding behavior in flies gave an interesting insight: that central and peripheral clocks both contribute to feeding, while under the fat body clock, there was no relation to feeding systems; instead, it was suggested that it may rely under light cues (Fulgham et al., 2021).

Although flies may seem very different from humans, there is no denying the reasons we use them as a model organism, since they are readily available for research. Due to similarities in circadian rhythm displays, ideas about how they relate to us can come about. Perhaps the idea that a molecular clock in flies may have its behavior affected due to light can correspond to the idea that humans, too, have our external behaviors affected by light.

In humans, previous research believed that only rods and cones responded to light as it went through the retina in the eye, but a third photoreceptor called intrinsically photosensitive retinal ganglia cells, or iPRGCs, has also been found to respond to light, despite not being part of the rod-cone system (Zuckerman, 2020). These photoreceptors have been found to target the suprachiasmatic nucleus, or SCN, which regulates and deals with the peripheral clocks of the circadian system; the effects light has on learning and mood relates to the idea that the SCN, under these photoreceptors, has its own independent function (Fernandez et al., 2018). Research has also shown that the iPRGCs have their own circuitry in the perihabenular nucleus of the thalamus, a region that connects to regulating mood (Fernandez et al., 2018).

When it comes to mood, specifically thinking about SAD, or seasonal affective disorder, a type of depression that individuals may experience when there is less natural light in their environment due to the fall and winter seasons, and how light can affect this disorder through iPRGCs, which are connected to the circadian system due to the idea that they target the SCN, can begin the discussion of the possible connection between circadian rhythms and mood. Light changes in the environment have been shown to affect mood; mice studies explain that there have been mood changes in the animals due to light disruption in the environment, and these changes usually take a bit of time, around two weeks, to occur (Zuckerman, 2020). This may help reveal why individuals with SAD have a hard time recognizing their changing mood; it is because it takes time for light to truly affect them (Zuckerman, 2020).

In terms of natural and artificial sunlight, the sun itself and going outside can help balance circadian rhythms, while bright artificial light, from electronics, for example, may hinder that balance (Zuckerman, 2020). The appeal of the affect different types of light might have on improving or impairing circadian rhythms and disorders such as SAD is one that must be investigated. In a world advancing in technology and global warming, would artificial or natural light contribute to a positive or negative outcome in individuals’ overall mood or individuals with disorders such as SAD? How would iPRGCs, which fall under the peripheral clock system, be affected by the different types of light, and would this research be beneficial to society in the future? These are only a few hypothetical questions, but in a world that is vastly changing, the answers may not be far behind.

References

Fernandez, D. C., Fogerson, P. M., Ospri, L. L, Thomsen, M. B., Layne, R. M., Severin, D., Zhan, J., Singer, J. H, Kirkwood, A., Zhao, H., Berson, D. M., & Hattar, S. (2018). Light affects mood and learning through distinct retina-brain pathways. Cell, 175(1), 71-84.

https://doi.org/10.1016/j.cell.2018.08.004

Fulgham, C. V., Dreyer, A. P., Nasseri, A., Miller, A. N., Love, J., Martin, M. M., Jabr, D. A., Saurabh, S., & Cavanaugh, D. J. (2021). Central and Peripheral Clock Control of Circadian Feeding Rhythms. Journal of Biological Rhythms, 36(6), 548-566. https://doi:10.1177/07487304211045835

Zuckerman, H. (2020). How does sunlight affect our mood? https://www.brainfacts.org/diseases-and-disorders/mental-health/2020/how-does-sunlight-affect-our-mood-120720

 

 

Domains and Processing Pathways Associated with Deficiencies in Top-Down Processing Associated with ADHD

  Top-down information processing occurs when the brain forms perceptions based on already stored information, allowing for increased processing speeds when receiving information from a sensory stimulus. More specifically, this form of processing contextualizes information from generalizations based on expectations and prior experiences to generate more specific inferences. For example, if one is presented with an image displaying only half of a computer, they would use previous knowledge through top-down processing to fill in the rest of the image based on previous knowledge and expectations. Individuals with Attention-Deficit/Hyperactivity Disorder (ADHD), however, demonstrate deficiencies with top-down processing. 

In the article, “Top-down attention modulates auditory-evoked neural responses in neurotypical, but not ADHD, young adults,” Kwasa et al. studied how individuals with ADHD demonstrate cognitive deficiencies with top-down processing when focusing attention on sensory stimuli. Specifically, the researchers investigated how these patients exhibit poorer performance compared to neurotypical individuals when completing tasks demanding of selectively attending to goal-relevant auditory stimulation - a challenging task requiring strong use of top-down attention. Participants listened to one of three concurrent, spatially separated streams of speech, and they were required to report the order of syllabi presented. As the participants were completing the task, the researchers were measuring electrophysiological correlates that are specific to top-down processing. Interestingly, they observed decreased N1 modulation (a negative-going ERP moment) in ADHD subjects compared to controls. Experimentation tested the ability to sustain attention on an individual speech stream as well as the ability to remain focused on the target while flexibly switching attention to a competing “interrupter” stimulus. According to the results of the study, attentional modulation indicative of top-down processing was weaker in participants with ADHD, demonstrating the differential abilities of listeners to modulate neural representations of sound with regard to the goals of the task. 

This weaker modulation of individuals with ADHD may also be implicated in symptoms of other behavioral disorders. In a related research study, “Distinct brain structure and behavior related to ADHD and conduct disorder traits,” Bayard et al. studied the comorbidity and shared genetic features of top-down dysregulation found in individuals with ADHD and Conduct Disorder (CD). Elaborating on previous studies, the researchers examined both non-emotional and emotional dysregulation as related to the deficiencies found in top-down processing pathways. Using magnetic resonance imaging (MRI) techniques, results of the study demonstrated that both ADHD and CD symptoms were correlated with overlapping activity in specific brain structures, notably a small structure of the prefrontal and anterior cingulate cortex. The researchers found that the gray matter volume and surface area of the region of interest found in the dorsolateral/dorsomedial prefrontal cortex and caudal anterior cingulate cortex demonstrated a negative association with ADHD symptoms while CD symptoms were being controlled, and the gray matter volume of the rostral anterior cingulate cortex demonstrated a negative association to CD symptoms while ADHD symptoms were being controlled. Similar findings were found when the researchers administered tests that required activity of the prefrontal and anterior cingulate regions. These data elaborate on deficiencies in top-down processing; performance on a Stop Signal test was specifically correlated with ADHD, while working memory was implicated with both ADHD and CD. Thus, the top-down processing deficiencies observed in individuals with ADHD demonstrate partial domains and dimensional capacities in the associated processing regulatory system. 

These two studies together provide greater insight into processing deficiencies associated with ADHD. Modulation of top-down processing involves varying domains and capacities that overlap with other neurological modalities, and the implications of the interactions of these pathways should be studied further. 

References

Bayard F;Nymberg Thunell C;Abé C;Almeida R;Banaschewski T;Barker G;Bokde ALW;Bromberg U;Büchel C;Quinlan EB;Desrivières S;Flor H;Frouin V;Garavan H;Gowland P;Heinz A;Ittermann B;Martinot JL;Martinot MP;Nees F;Orfanos DP;Paus T;Poustka L;Conrod P;Stringari. (n.d.). Distinct brain structure and behavior related to ADHD and conduct disorder traits. Molecular psychiatry. Retrieved March 4, 2022, from https://pubmed.ncbi.nlm.nih.gov/30108313/ 

Kwasa, J. A., Noyce, A. L., Torres, L. M., & Shinn-Cunningham, B. G. (2021). Top-down attention modulates auditory-evoked neural responses in neurotypical, but not ADHD, young adults. https://doi.org/10.1101/2021.02.11.430824