January 9th, 2023 

Memories can be laid down well without sleep attached to it according to a new study in PNAS. It has long been said that sleep is key to culling neurons that are related to memories that are unimportant and also increasing the quality of the neurons for memories that we need to keep, while sleep deprivation disrupts this reality. The authors of this study looked at two groups of rats show a novel object and tracked the quality of the memory formation. They state: "Long-term memories are considered to be optimally formed during sleep, but they may also be formed during wakefulness. Using behavioral indicators dissociating object and context memory in a novel-object recognition (NOR) paradigm, in combination with pharmacological inhibition of hippocampal activity

during postencoding consolidation, we show that, in contrast to sleep consolidation, wake consolidation does not comprise the spatial–contextual integration of the NOR memory and is impaired by ongoing hippocampal activity.

Accordingly, remote NOR memory after wake consolidation was even superior to that after sleep consolidation when tested in a context different from encoding. Our study directly comparing sleep and wake-dependent consolidation demonstrates that memories consolidated during wake and sleep differ in quality, but not necessarily in strength." (Sawangjit et. al. 2022)

2) We all know the sleep deprived child for the inability to control emotions and actions in a neutral grounded way. What does sleep loss do to adults behavior? "Sleep loss is known as a robust modulator of emotional reactivity, leading to increased anxiety and stress elicited by seemingly minor triggers. In this work, we aimed to portray the neural basis of these emotional impairments and their possible association with frontal regulation of emotional processing, also known as cognitive control of emotion. Using specifically suited EEG and fMRI tasks, we were able to show that sleep deprivation alters emotional reactivity by triggering enhanced processing of stimuli regarded previously as neutral. These changes were further accompanied by diminished frontal connectivity, reduced REM sleep, and poorer performance. Therefore, we suggest that sleep loss alters emotional reactivity by lowering the threshold for emotional activation, leading to a maladaptive loss of emotional neutrality." (Simon et. al. 2015)

This is so important to understand from a parental and relational perspective. Those humans that are sleep deprived and emotionally dys-regulated end up having a much more difficult time holding and maintaining normal relationships. They end up being lonely in the long run which could become a loop effect on sleep deprivation which in turn could and likely will lead to a mood depressed state. I think of screens, phones, video games and other sleep disruptors here.

"People are less interested in social interaction when they’re sleep-deprived. For example, we designed a task where an experimenter and participant would face each other, and they would walk toward each other. The participant would decide when someone got too close, and we would measure that distance. Consistently, when people were sleep-deprived, they preferred others to be farther away. Mood may play a part in the social consequences of sleep loss, but it’s not the whole story. We’ve controlled for mood in studies of social behavior and seen that social withdrawal is not just an effect of mood. We’ve also found that sleep deprivation reduces activity in what’s known as the theory of mind network in the brain. These are areas that help us think about other people—what they might want, what they’re like, and how they are similar to or different from ourselves." "We’re such social beings. Why would our sleepy brain shut down the network that helps us connect with others? The brain and body need sleep so much that they start letting go of whatever we don’t immediately need once sleep is missing. In nature, the only time you see animals sleep-deprived is when they’re migrating, they just had a baby or they’re starving. So being sleep-deprived is really a stress signal that makes us want to accumulate as much food as we can and be more alert to threats. We don’t have the capacity for anything more than that. The more time you spend awake, the more sleep becomes the one thing that you need to focus on. Everything else just goes in the background." (Yuhas D. 2022)

 

3) Gaslighting is a real phenomenon that is gaining ground in the scientific literature as a way for one member of a group or relationship to make the oppressed upon in the situation believe that their thoughts are irrational or untrue. The use of this technique, if conscious, is diabolical in its scope and effect. For one to gaslight another is to consciously abuse the person psychologically to gain a power gradient and hurt the other. This is nothing short of evil.

On the other hand, it is a tricky reality in truth for many relationships as the gaslighting perception by the oppressed may be a feeling and in truth a judgement call and not a nefarious event to actually gas light. Think of a child saying that they felt x occurred by your actions when it clearly did not. How is one to handle it? Do you agree with their feelings and assume the guilt of an untruth while you hold space for them to move through the event as perceived. Do you not admit the event as truth, but instead let it exist while you hold space for them to work through it nonetheless. Do you posture and deny to everyone's loss? I submit that option two seems the most relational.

Read the Sweet article for a deeper dive here.

4) In an opinion piece in the NYTimes, we see an article about the truth about food and health where it lies with the overconsumption of animals as a food source. (Grunwald M. 2022) We certainly as a society consume far too much animal meat protein on a historical basis to the detriment of the forests and other land that is taken for grazing. Humans are great at doing what they wish despite the ramifications to the planet and other species. As a provider of care, my belief is that the preponderance of anthropological and medical data leads me to think that we would be better off with meat a few times a week varied across different species as eaten. I do not think that there is enough data to make any other conclusions. I will submit that I eat way too much animal protein.

My 2 cents.

5) Devices and young children: "In this cohort study of 422 parents and 422 children, increased use of mobile devices for calming children aged 3 to 5 years was found to be associated with decreased executive functioning and increased emotional reactivity at baseline; however, only emotional reactivity had bidirectional, longitudinal associations with device use for calming at 3 and 6 months of follow-up. The associations were found to be increased in boys and children with higher temperamental surgency." (Radesky et. al. 2022)

In our clinic, we see frequent use of screens to babysit children while another is examined/discussed. While this seems innocuous in this one instance, the frequency of use at other times may and likely will come back to be a net negative on emotional health. What are some solutions?

Dr. Radesky recommends:

• "Sensory techniques: Young kids have their own unique profiles of what types of sensory input calms them down. This could include swinging, hugging or pressure, jumping on a trampoline, squishing putty in their hands, listening to music or looking at a book or sparkle jar. If you see your child getting antsy, channel that energy into body movement or sensory approaches.
• Name the emotion and what to do about it: When parents label what they think their child is feeling, they both help the child connect language to feeling states, but they also show the child that they are understood. The more parents can stay calm, they can show kids that emotions are "mentionable and manageable," as Mister Rogers used to say.
• Use color zones: When children are young, they have a hard time thinking about abstract and complicated concepts like emotions. Color zones (blue for bored, green for calm, yellow for anxious/agitated, red for explosive) are easier for kids to understand and can be made into a visual guide kept on the fridge, and help young children paint a mental picture of how their brain and body is feeling. Parents can use these color zones in challenging moments ("you are getting wiggly and in the yellow zone -- what can you do to get back to green?")
• Offer replacement behaviors: Kids can show some pretty negative behaviors when they are upset, and it's a normal instinct to want it to just stop. But those behaviors are communicating emotions -- so kids might need to be taught a safer or more problem-solving replacement behavior to do instead. This might include teaching a sensory strategy ("hitting hurts people; you can hit this pillow instead") or clearer communication ("if you want my attention, just tap my arm and say 'excuse me, mom.'")" (Mostafavi O. 2022)

6) APOE4 genotype is highly associated with Alzheimers disease according to many studies over the years. Now we have a subgroup analysis that changes this narrative. " In this genetic association study, a novel variant associated with AD was identified: R251G always coinherited with ε4 on the APOE gene, which mitigates the ε4-associated AD risk. The protective effect of the V236E variant, which is always coinherited with ε3 on the APOE gene, was also confirmed. The location of these variants confirms that the carboxyl-terminal portion of apoE plays an important role in AD pathogenesis. The large risk reductions reported here suggest that protein chemistry and functional assays of these variants should be pursued, as they have the potential to guide drug development targeting APOE." (Guen et. al. 2022)

7) More one APOE4. In a study in the Journal Science Translational Medicine we see a study looking at the defective lipid metabolism in glial cells of humans. These immune cells in the brain accumulated extra triglycerides which could impair activity, a hallmark of neurodegenerative disease. The use of Choline supplementation was capable of reversing these negative effects despite the APOE4 single nucleotide polymorphism.

From the study: "The E4 allele of the apolipoprotein E gene (APOE) has been established as a genetic risk factor for many diseases including cardiovascular diseases and Alzheimer’s disease (AD), yet its mechanism of action remains poorly understood. APOE is a lipid transport protein, and the dysregulation of lipids has recently emerged as a key feature of several neurodegenerative diseases including AD. However, it is unclear how APOE4 perturbs the intracellular lipid state. Here, we report that APOE4, but not APOE3, disrupted the cellular lipidomes of human induced pluripotent stem cell (iPSC)–derived astrocytes generated from fibroblasts of APOE4 or APOE3carriers, and of yeast expressing human APOE isoforms. We combined lipidomics and unbiased genome-wide screens in yeast with functional and genetic characterization to demonstrate that human APOE4 induced altered lipid homeostasis. These changes resulted in increased unsaturation of fatty acids and accumulation of intracellular lipid droplets both in yeast and in APOE4-expressing human iPSC-derived astrocytes. We then identified genetic and chemical modulators of this lipid disruption. We showed that supplementation of the culture medium with choline (a soluble phospholipid precursor) restored the cellular lipidome to its basal state in APOE4-expressing human iPSC-derived astrocytes and in yeast expressing human APOE4. Our study illuminates key molecular disruptions in lipid metabolism that may contribute to the disease risk linked to the APOE4 genotype. Our study suggests that manipulating lipid metabolism could be a therapeutic approach to help alleviate the consequences of carrying the APOE4 allele." (Sienski et. al. 2022)

This is critical data. Coupled to the study on APOE4 subgroups, we see a picture whereby we can genotype the population, use choline in those at risk and track risk reduction.

Always so much to think about,

Dr. M

Sawangjit PNAS
Yuhas Scientific American
Simon J Neuroscience
Sweet Scientific American
Grunwald NYTimes
Radesky JAMA Pediatrics
Mostafavi Science Daily
Guen JAMA Neurology
Sienski Science Translational Medicine