Researchers identify biomarker of cognitive fatigue in multiple sclerosis and long Covid

 Have your competent? doctors and hospital get research going on biomarkers of post stroke fatigue, so we can get protocols created that remove that fatigue! My idiot of a doctor just said I needed more cardiovascular fitness, i.e. more exercise.  He never tested my fitness level which was at the kevel of an athlete.

3 years post stroke at a physical I had a resting heart rate of 54 at age 53, level of an athlete. My doctor asked what exercises I was doing; 'I've done no exercises for the past 3 years'.  And now 20 years past the stroke my fitness has declined a bit, ALL BECAUSE MY STROKE MEDICAL 'PROFESSIONALS' COMPLETELY FAILED AT GETTING ME 100% RECOVERED!  Still managed to get to Tiger's Nest in Bhutan at 10,240 feet in 2023

Researchers identify biomarker of cognitive fatigue in multiple sclerosis and long Covid

New work could pave the way for objective assessment of cognitive fatigue across multiple conditions.

For many people with post-Covid-19 syndrome, also known as 'long Covid', the mental exhaustion, difficulties with concentrating, and impaired cognitive performance that characterise cognitive fatigue can be some of the most disabling symptoms. Cognitive fatigue is also commonly reported by people suffering from other post-viral conditions, as well as conditions such as multiple sclerosis (MS).

However, the underlying causes of this kind of fatigue remain elusive, write Stefanie Linnhoff at Otto-von-Guericke University, Germany, and colleagues in a recent paper in Psychological Medicine. That's largely down to its "subjective and often invisible nature", along with a lack of objective diagnostic markers, they write. In their paper, though, they describe what they believe to be a marker — one that they think could be used to monitor cognitive fatigue in people with a range of different disorders.

Linnhoff and her colleagues recruited 119 participants for their study. Of these, 36 were healthy controls, 33 had 'long Covid-related fatigue', and 50 had MS. All completed a questionnaire that asked about cognitive fatigue, and this led the team to identify 23 of the MS group as being fatigued, and the rest as non-fatigued. The team then used EEG to monitor activity in the participants' brains while they spent three minutes at rest with their eyes closed.

When the researchers analysed the EEG data, they were on the look-out for something called 'aperiodic activity' — irregular electrical signals that were once dismissed as a kind of background noise in the brain, but are now recognised as representing the overall balance between excitation and inhibition in neural networks.

Two neurotransmitters are crucial for this balance; the neurotransmitter glutamate increases excitation (meaning signals are more likely to pass between neurons), while GABA does the opposite. Having the right 'excitation/inhibition (E/I) balance' is important for healthy brain function, and, as the team notes, disruptions to this balance have been linked to various neurological and psychiatric disorders, including MS.

When the team compared the subjective fatigue scores from the participants with the EEG recordings, they found that higher fatigue was associated with lower, flatter, aperiodic values, reflecting a shift towards excitatory activity, in the frontal region of the brain. The long Covid and the fatigued — but not the non-fatigued — MS participants had similar aperiodic activity.

This type of activity in one area of the frontal region, in particular, seemed to be especially tied to fatigue scores. This was the left dorsolateral prefrontal cortex, an area that is important for a number of cognitive functions, including sustained attention and cognitive control. The team writes: "This… points to the dlPFC as a potential common hub of vulnerability in fatigue, possibly reflecting a final common pathway of disrupted cognitive control due to impaired E/I balance."

Further work would be needed to explore whether changes to the E/I balance cause cognitive fatigue, or whether the opposite is true and fatigue drives changes in this balance — as well as to explore whether, as the team suspects, these findings will be replicated in people with cognitive fatigue associated with other conditions. Teams elsewhere are also investigating other potential brain markers of cognitive fatigue; in a recent study of groups of people with myalgic encephalomyelitis and long Covid, for example, Maira Inderyas at Griffith University in Australia and her colleagues reported finding reduced connectivity between various brain regions, which they linked to blunted motivation as well as cognition.

Linnhoff and her colleagues now hope that their findings will pave the way for new, objective ways of assessing cognitive fatigue in patients, as well as for evaluating the effectiveness of treatments.

Read the paper in full:
Linnhoff, S., Kadosh, R. C., & Tino Zaehle. (2026). EEG-based frontal excitation/inhibition balance as an objective biomarker for cognitive fatigue across multiple sclerosis and Long COVID. Psychological Medicine, 56, e21–e21. https://doi.org/10.1017/s0033291725103024

Loss of brain interneurons linked to cognitive deficits in aging

Is your doctor checking on this before automatically blaming the stroke for your cognitive deficits?

Loss of brain interneurons linked to cognitive deficits in aging

Reviewed by Megan Craig, M.Sc.Sep 28 2023

Normal aging is usually associated with a decline in memory, although it is unclear what factors play a role. In a new study, researchers studied specific interneurons, which serve as communication centers that connect other neurons, in the regions of the brain that are important for learning and memory.

Increasing age places people at risk, whether it is because of a normal decrease in cognitive ability or due to postoperative cognitive disorders. In the latter, the deficits can persist for many months after surgery especially when the patients are older than 60. Unfortunately, the underlying cellular mechanisms that cause these impairments are largely unknown.

Previous studies have shown that the region of the brain that is associated with learning and memory-;the hippocampus-; decreases in volume with age. Additionally, the levels of the molecule -aminobutyric acid, or GABA, and some of the interneurons that release it are also affected.

In the present study, the researchers focused on the hippocampal interneurons in a specific region, called the hilus of the dentate gyrus, that are characterized by their expression of somatostatin. This hormone has the ability to counteract the effects of growth hormones elsewhere in the body.

In the past, other researchers have found that one of the differences between cognitively impaired and unimpaired rats was that the former had a lower number of somatostatin-positive interneurons in the hilus of the dentate gyrus. We wanted to further investigate whether a loss of these neurons is really responsible for cognitive deficits, and whether it could thus serve as a model of aging in the hippocampus."

Uwe Rudolph (GNDP), professor of comparative biosciences

The researchers decreased the numbers of somatostatin-positive interneurons in the hippocampus of mice by using a toxin. They injected this toxin into the dentate hilus, so that the toxin would only be expressed in the somatostatin-positive interneurons, killing approximately 50% of these cells. Starting 3 weeks later, they conducted behavioral studies to test the learning abilities and memory of the mice.

The mice underwent three types of tests: whether they could remember and differentiate novel objects from familiar ones, navigate mazes using their short-term memories, and use their spatial learning to find a hidden platform in a pool of water. In all three cases, the mice that had decreased levels of somatostatin-positive interneurons struggled compared to those that did not receive the toxin.

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The researchers also looked for changes in cellular signals that occur due to lower levels of somatostatin-positive interneurons. To do so, they focused on the microglia, which are immune cells that are among the first to respond when something goes wrong in the brain.

"We looked at microglial activation, which is a hallmark of the inflammation that is associated with aging and memory impairment," said Rajasekar Nagarajan, a postdoctoral researcher in the Rudolph lab. "We saw increased activation of microglia in the hippocampus of the mice that were injected with the toxin, even outside of the dentate gyrus."

In addition to determining the status of microglia, the team measured a protein called brain-derived neurotrophic factor, which is active in the hippocampus and plays a role in long-term memory. They found that there were lower BDNF levels in the hippocampal tissue of the toxin-injected mice. Furthermore, the researchers also found that these mice had fewer hippocampal dendritic spines, which are critical for learning and memory.

Unsurprisingly for the researchers, the results seen with the toxin-injected mice were essentially the same as with aged mice that were 18-19 months old and had not been injected with the toxin.

"18-month-old mice correspond to an age of approximately 60 years in humans. It roughly fits the time point at which we know that people more frequently develop neurocognitive deficits in response to surgery and anesthesia," Rudolph said. "Our results have shown that using this toxin to reduce the number of somatostatin-positive interneurons is sufficient to cause effects that resemble cognitive deficits in aging."

The researchers are excited that they can use these techniques to investigate aging-related defects without waiting for the mice to grow old, which is an expensive and time-consuming undertaking. "We will be using this method as a model to test which experimental compounds can be used to prevent or reverse both age-related and post-operative cognitive impairments," Nagarajan said.

Source:

Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign

Journal reference:

Nagarajan, R., et al. (2023) Genetic Ablation of Dentate Hilar Somatostatin-Positive GABAergic Interneurons is Sufficient to Induce Cognitive Impairment. Molecular Neurobiology. doi.org/10.1007/s12035-023-03586-3.

New discovery can revolutionize the diagnosis and treatment of Alzheimer's disease

Do you really think you have a competent doctor and hospital following this closely because of your substantial risks of dementia? WELL I DOUBT IT! 

Your risk of dementia, has your doctor told you of this?

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.`    

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

The latest here:

New discovery can revolutionize the diagnosis and treatment of Alzheimer's disease

Recently, a team of South Korean scientists led by Director C. Justin LEE of the Center for Cognition and Sociality within the Institute for Basic Science made a new discovery that can revolutionize both the diagnosis and treatment of Alzheimer's Disease. The group demonstrated a mechanism where the astrocytes in the brain uptake elevated levels of acetates, which turns them into hazardous reactive astrocytes. They then went on further to develop a new imaging technique that takes advantage of this mechanism to directly observe the astrocyte-neuron interactions.

Alzheimer's disease (AD), one of the major causes of dementia, is known to be associated with neuroinflammation in the brain. While traditional neuroscience has long believed that amyloid beta plaques is been the cause, treatments that target these plaques have had little success in treating or slowing the progression of Alzheimer's disease.

On the other hand, Director C. Justin LEE has been a proponent of a novel theory that reactive astrocytes are the real culprit behind Alzheimer's disease. Reactive astrogliosis, a hallmark of neuroinflammation in AD, often precedes neuronal degeneration or death.

Lee's research team previously reported that reactive astrocytes and the monoamine oxidase B (MAO-B) enzyme within these cells can be utilized as therapeutic targets for AD. Recently, they also confirmed the existence of a urea cycle in astrocytes and demonstrated that the activated urea cycle promotes dementia. However, despite the clinical importance of reactive astrocytes, brain neuroimaging probes that can observe and diagnose these cells at a clinical level have not yet been developed.

In this latest research, Lee's team used positron emission tomography (PET) imaging with radioactive acetate and glucose probes (¹¹C-acetate and ¹⁸F-FDG) to visualize the changes in neuronal metabolism in AD patients.

This study demonstrates significant academic and clinical value by directly visualizing reactive astrocytes, which have recently been highlighted as a main cause of AD."

Dr. Nam Min-Ho, one of the first authors of the paper

Furthermore, they demonstrated that acetate, the main component of vinegar, is responsible for promoting reactive astrogliosis, which induces putrescine and GABA production and leads to dementia. First, the researchers demonstrated that reactive astrocytes excessively uptake acetate through elevated monocarboxylate transporter-1 (MCT1) in rodent models of both reactive astrogliosis and AD. It was discovered that the elevated acetate uptake is associated with reactive astrogliosis and boosts the aberrant astrocytic GABA synthesis when amyloid-beta, a well-known toxin protein in AD, is present.

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The researchers showed that PET imaging with ¹¹C-acetate and ¹⁸F-FDG can be used to visualize the reactive astrocyte-induced acetate hypermetabolism and associated neuronal glucose hypometabolism in the brains with neuroinflammation and AD. Moreover, when the researchers inhibited reactive astrogliosis and astrocytic MCT1 expression in the AD mouse model, they were able to reverse these metabolic alterations.

Dr. YUN Mijin commented, "Reactive astrocytes showed metabolic abnormalities that excessively uptake acetate compared to normal state. We found that the acetate plays an important role in promoting astrocytic inflammatory responses."

By using this new imaging strategy, the group discovered that alterations in acetate and glucose metabolism were consistently observed in the AD mouse model and human AD patients. They were able to confirm that a strong correlation exists between the patient's cognitive function and the PET signals of both ¹¹C-acetate and ¹⁸F-FDG. These results suggest that acetate, previously considered an astrocyte-specific energy source, can facilitate reactive astrogliosis and contribute to the suppression of neuronal metabolism.

Dr. RYU Hoon remarked, "By demonstrating that acetate not only acts as an energy source for astrocytes but also facilitates reactive astrogliosis, we suggested a new mechanism that induces reactive astrogliosis in brain diseases."

Until now, amyloid beta (Aβ) has been suspected as the main cause of AD, and thus they have been the main focus of most dementia research. Unfortunately, PET imaging targeting Aβ has had limitations in diagnosing patients, and drugs aimed at removing it as a target for AD treatment have all failed so far. However, this study offers us a new possibility of using ¹¹C-acetate and ¹⁸F-FDG PET imaging for early diagnosis of AD. In addition, the newly discovered mechanism of reactive astrogliosis through acetate and MCT1 transporter suggests a new target for AD treatment.

Dr. C. Justin LEE stated, "We confirmed a significant recovery when inhibiting MCT1, astrocyte-specific acetate transport, in an AD animal model," and added, "We expect MCT1 can be a new therapeutic target for AD."

Source:

Institute for Basic Science

Journal reference:

Nam, M.-H., et al. (2023). Visualizing reactive astrocyte-neuron interaction in Alzheimer’s disease using 11C-acetate and 18F-FDG. Brain. doi.org/10.1093/brain/awad037.

Modified Mediterranean ketogenic diet may improve brain health

You'll have to ask your doctor to get the specific protocol on this. The Mediterranean diet has nothing specific in it.

Modified Mediterranean ketogenic diet may improve brain health 

Key takeaways:

• A modified Mediterranean ketogenic diet may reduce the risk for Alzheimer’s disease.
• Researchers said that the findings offer critical insight into how diet could improve brain health.

A modified Mediterranean ketogenic diet was associated with changes in a biological pathway linked to Alzheimer’s disease among older adults with mild cognitive impairment, according to study results published in Alzheimer’s and Dementia.

The ketogenic diet has emerged as a potential candidate for Alzheimer’s disease treatment because of its known protective effects for seizures and metabolic dysregulation, Amanda Hazel Dilmore, a PhD student in Rob Knight's lab at the University of California, San Diego, and colleagues wrote.

A modified Mediterranean ketogenic diet may be beneficial for older adults with mild cognitive impairment, according to researchers. Image: Adobe Stock

“The ketogenic diet is a candidate therapeutic for Alzheimer’s disease because of its ability to improve mitochondrial function and cerebral bioenergetics, enhance autophagy, and reduce oxidative stress,” they wrote. “It also reduces neuronal hyperexcitability and leads to improved amyloid and tau regulation, substantiating its potential use for cognitive impairment.”

Dilmore and colleagues added that gut microbiota are critical for ketogenic diet-mediated protection against seizures and modulation of bile acids — a major factor in cholesterol metabolism. Interest in those relationships, they wrote, was the catalyst for their analysis of gut microbiota and metabolites related to cognitive status after a ketogenic diet intervention compared with a low-fat-diet intervention.

“We hope that better understanding this complex relationship between diet, cognitive status and gut health will lead to new interventions to prevent and treat Alzheimer’s disease,” Suzanne Craft, PhD, professor of gerontology and geriatric medicine at Wake Forest University School of Medicine, said in a press release.

The researchers randomly assigned 20 prediabetic adults with either normal cognition or mild cognitive impairment (MCI) to a high-fat modified Mediterranean ketogenic diet (MMKD) or a low-fat American Heart Association diet for 6 weeks. After a 6-week washout period, the participants then began the alternate diet. To analyze changes in gut microbiome and metabolome, the researchers collected stool samples at five timepoints throughout the interventions.

Dilmore, Craft and colleagues found that, through modulation of GABA levels and gut-transit time, the MMKD may help older adults with MCI. (May help is not good enough! Tell us EXACTLY what will help! Do your research properly to provide answers!)

“Broadly, our investigation demonstrated that controlled changes in diet led to widespread changes in the microbiome and metabolome over time,” they wrote.

More specifically, the researchers found that those with MCI on the MMKD had lower levels of GABA — an inhibitory neurotransmitter — and GABA-producing microbes. They also had higher levels of GABA-regulating microbes. Notably, low levels of GABA have been linked to conditions like Alzheimer’s disease.

“Our study is the first to show that diet modulates GABA differently in MCI,” Craft said in the release.

The researchers also noted that those with MCI who also had curcumin in their diet had an altered bile acid pool and lower levels of bile salt hydrolase-containing microbes, which they wrote suggests reduced gut motility.

“Gut microbiota are known to modulate the bile acid pool; given that bile acids are the primary agent of cholesterol depletion in the brain, gut microbiota-induced changes to the bile acid pool may mitigate the dysregulation of cholesterol metabolism,” they wrote.

Dilmore, Craft and colleagues acknowledged that the study was limited because of its small sample size and “relatively brief intervention period,” but acknowledged the importance of their results.

“These findings provide crucial insight into how diet may affect the microbiome and improve brain health,” Craft said in the release. “Larger studies are needed to assess the role diet interventions play in patients with cognitive impairment.”

References:

• Dilmore AH, et al. Alzheimers Dement. 2023;doi:10.1002/alz.13007.
• Modified Mediterranean ketogenic diet may benefit adults at risk for Alzheimer's disease. https://www.eurekalert.org/news-releases/985220. Published April 5, 2023. Accessed April 6, 2023.

EXPRESS: Differences in outcomes following an intensive upper-limb rehabilitation programme for patients with common CNS-acting drug prescriptions

 You'll have to have your doctor find the protocols for this. Bad research since they didn't put those protocols in a publicly available database

EXPRESS: Differences in outcomes following an intensive upper-limb rehabilitation programme for patients with common CNS-acting drug prescriptions

Show all authors

Ainslie Johnstone, Fran Brander, Kate Kelly , ...

First Published March 16, 2021 Research Article 

https://doi.org/10.1177/17474930211006287

Article information

 

Abstract

Difficulty using the upper-limb is a major barrier to independence for many patients post-stroke or brain injury. High dose rehabilitation can result in clinically significant improvements in function even years after the incident, however there is still high variability in patient responsiveness to such interventions that cannot be explained by age, sex or time since stroke.

This retrospective study investigated whether patients prescribed certain classes of CNS-acting drugs - GABA agonists, antiepileptics and antidepressants-differed in their outcomes on the 3 week intensive Queen Square Upper-Limb (QSUL) programme.

For 277 stroke or brain injury patients (167 male, median age 52 years (IQR 21), median time since incident 20 months (IQR 26)) upper-limb impairment and activity was assessed at admission to the programme and at 6 months post-discharge, using the upper limb component of the Fugl-Meyer (FM), Action Research Arm Test (ARAT), and Chedoke Arm and Hand Activity Inventory (CAHAI). Drug prescriptions were obtained from primary care physicians at referral. Specification curve analysis (SCA) was used to protect against selective reporting results and add robustness to the conclusions of this retrospective study.

Patients with GABA agonist prescriptions had significantly worse upper-limb scores at admission but no evidence for a significant difference in programme-induced improvements was found. Additionally, no evidence of significant differences in patients with or without antiepileptic drug prescriptions on either admission to, or improvement on, the programme was found in this study. Whereas, though no evidence was found for differences in admission scores, patients with antidepressant prescriptions experienced reduced improvement in upper-limb function, even when accounting for anxiety and depression scores.

These results demonstrate that, when prescribed typically, there was no evidence that patients prescribed GABA agonists performed worse on this high-intensity rehabilitation programme. Patients prescribed antidepressants, however, performed poorer than expected on the QSUL rehabilitation programme. While the reasons for these differences are unclear, identifying these patients prior to admission may allow for better accommodation of differences in their rehabilitation needs.

Keywords GABA agonists, Rehabilitation, antidepressants, antiepileptic, drugs, motor function, upper-limb impairmentAccess Options

 

The Influence of Primary Motor Cortex Inhibition on Upper Limb Impairment and Function in Chronic Stroke: A Multimodal Study

So the objective had nothing to do with getting survivors recovered. Not even barely tangentially.

The Influence of Primary Motor Cortex Inhibition on Upper Limb Impairment and Function in Chronic Stroke: A Multimodal Study

Show all authors

Ronan A. Mooney, Suzanne J. Ackerley, PhD, Deshan K. Rajeswaran, MD, ...

First Published February 11, 2019 Research Article

https://doi.org/10.1177/1545968319826052

Article information

Abstract

Background. Stroke is a leading cause of adult disability owing largely to motor impairment and loss of function. After stroke, there may be abnormalities in γ-aminobutyric acid (GABA)-mediated inhibitory function within primary motor cortex (M1), which may have implications for residual motor impairment and the potential for functional improvements at the chronic stage.
Objective. To quantify GABA neurotransmission and concentration within ipsilesional and contralesional M1 and determine if they relate to upper limb impairment and function at the chronic stage of stroke.  
Methods. Twelve chronic stroke patients and 16 age-similar controls were recruited for the study. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Threshold tracking paired-pulse transcranial magnetic stimulation protocols were used to examine short- and long-interval intracortical inhibition and late cortical disinhibition. Magnetic resonance spectroscopy was used to evaluate GABA concentration.
Results. Short-interval intracortical inhibition was similar between patients and controls (P = .10). Long-interval intracortical inhibition was greater in ipsilesional M1 compared with controls (P < .001). Patients who did not exhibit late cortical disinhibition in ipsilesional M1 were those with greater upper limb impairment and worse function (P = .002 and P = .017). GABA concentration was lower within ipsilesional (P = .009) and contralesional (P = .021) M1 compared with controls, resulting in an elevated excitation-inhibition ratio for patients.
Conclusion. These findings indicate that ipsilesional and contralesional M1 GABAergic inhibition are altered in this small cohort of chronic stroke patients. Further study is warranted to determine how M1 inhibitory networks might be targeted to improve motor function.

Alpha-Linolenic Acid Treatment Reduces the Contusion and Prevents the Development of Anxiety-Like Behavior Induced by a Mild Traumatic Brain Injury in Rats

Don't do this without a doctors prescription. 

Alpha-Linolenic Acid Treatment Reduces the Contusion and Prevents the Development of Anxiety-Like Behavior Induced by a Mild Traumatic Brain Injury in Rats

• Authors
• Authors and affiliations

• Taiza H. Figueiredo
• Carolina L. Harbert
• Volodymyr Pidoplichko
• Camila P. Almeida-Suhett
• Hongna Pan
• Katia Rossetti
• Maria F. M. Braga
• Ann M. MariniEmail author

• Taiza H. Figueiredo
  • 1
• Carolina L. Harbert
  • 1
• Volodymyr Pidoplichko
  • 1
• Camila P. Almeida-Suhett
  • 1
• Hongna Pan
  • 2
• Katia Rossetti
  • 1
• Maria F. M. Braga
  • 1
• Ann M. Marini
  • 2
  Email author

1. 1.Department of Anatomy, Physiology and GeneticsUniformed Services University of the Health SciencesBethesdaUSA
2. 2.Department of Neurology and Program in NeuroscienceUniformed Services University of the Health SciencesBethesdaUSA

Article

First Online:

26 August 2017

• 2 Shares
• 24 Downloads

Abstract

Approximately, 1.7 million Americans suffer a TBI annually and TBI is a major cause of death and disability. The majority of the TBI cases are of the mild type and while most patients recover completely from mild TBI (mTBI) about 10% result in persistent symptoms and some result in lifelong disability. Anxiety disorders are the second most common diagnosis post-TBI. Of note, TBI-induced anxiety disorders are difficult to treat and remain a chronic condition suggesting that new therapies are needed. Previous work from our laboratory demonstrated that a mild TBI induced an anxiety-like phenotype, a key feature of the human condition, associated with loss of GABAergic interneurons and hyperexcitability in the basolateral amygdala (BLA) in rodents 7 and 30 days after a controlled cortical impact (CCI) injury. We now confirm that animals display significantly increased anxiety-like behavior 30 days after CCI. The anxiety-like behavior was associated with a significant loss of GABAergic interneurons and significant reductions in the frequency and amplitude of spontaneous and miniature GABA_A-receptor-mediated inhibitory postsynaptic currents (IPSCs) in the BLA. Significantly, subchronic treatment with alpha-linolenic acid (ALA) after CCI prevents the development of anxiety-like behavior, the loss of GABAergic interneurons, hyperexcitability in the BLA and reduces the impact injury. Taken together, administration of ALA after CCI is a potent therapy against the neuropathology and pathophysiological effects of mTBI in the BLA.

A Single Bout of High-Intensity Interval Training Improves Motor Skill Retention in Individuals With Stroke

Well fuck, then write this up into a stroke protocol, if you don't you are part of the problem and should remove yourself from this area.  This research seems to be useless since the background doesn't match what the objective and method says.  Would this be better if done in acute stroke rather than chronic? We'll never know.
http://journals.sagepub.com/doi/abs/10.1177/1545968317718269

Show all authors

Jean-Francois Nepveu, MSc, Alexander Thiel, MD, PhD, Ada Tang, PhD, ...

First Published July 8, 2017 Research Article

Download PDF	Article information

Abstract

Background. One bout of high-intensity cardiovascular exercise performed immediately after practicing a motor skill promotes changes in the neuroplasticity of the motor cortex and facilitates motor learning in nondisabled individuals.
Objective. To determine if a bout of exercise performed at high intensity is sufficient to induce neuroplastic changes and improve motor skill retention in patients with chronic stroke.  
Methods. Twenty-two patients with different levels of motor impairment were recruited. On the first session, the effects of a maximal graded exercise test on corticospinal and intracortical excitability were assessed from the affected and unaffected primary motor cortex representational area of a hand muscle with transcranial magnetic stimulation. On the second session, participants were randomly assigned to an exercise or a nonexercise control group. Immediately after practicing a motor task, the exercise group performed 15 minutes of high-intensity interval training while the control group rested. Twenty-four hours after motor practice all participants completed a test of the motor task to assess skill retention.  
Results. The graded exercise test reduced interhemispheric imbalances in GABA_A-mediated short-interval intracortical inhibition but changes in other markers of excitability were not statistically significant. The group that performed high-intensity interval training showed a better retention of the motor skill.  
Conclusions. The performance of a maximal graded exercise test triggers only modest neuroplastic changes in patients with chronic stroke. However, a single bout of high-intensity interval training performed immediately after motor practice improves skill retention, which could potentially accelerate motor recovery in these individuals.

60 references supporting this. 

Love it or hate it: Marmite may affect brain function

Ask your doctor what EXACTLY they are doing to see what help this might be for stroke recovery. Not doing one damn thing should be grounds for firing.  Dead wood needs to be removed before it affects the health and recovery of your children and grandchildren from stroke. Do not do on your own.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=174140&CultureCode=en
Scientists at the University of York have discovered a potential link between eating Marmite and activity in the brain, through the apparent increase of a chemical messenger associated with healthy brain function.

Participants consuming a teaspoon of Marmite every day for a month, compared to a control group who consumed peanut butter, showed a substantial reduction of around 30 per cent in their brain’s response to visual stimuli, measured by recording electrical activity using electroencephalography (EEG).

Researchers think this may be due to the prevalence of vitamin B12 in Marmite increasing levels of a specific neurotransmitter – known as GABA – in the brain.

GABA inhibits the excitability of neurons in the brain, with the chemical acting to ‘turn down the volume’ of neural responses in order to regulate the delicate balance of activity needed to maintain a healthy brain.

As Marmite consumption appears to increase GABA levels, this study is the first to show that dietary intervention may affect these neural processes. GABA imbalances are also associated with a variety of neurological disorders.

Anika Smith, PhD student in York’s Department of Psychology and first author of the study, said: “These results suggest that dietary choices can affect the cortical processes of excitation and inhibition - consistent with increased levels of GABA – that are vital in maintaining a healthy brain.

“As the effects of Marmite consumption took around eight weeks to wear off after participants stopped the study, this suggests that dietary changes could potentially have long-term effects on brain function.

“This is a really promising first example of how dietary interventions can alter cortical processes, and a great starting point for exploring whether a more refined version of this technique could have some medical or therapeutic applications in the future. Of course, further research is needed to confirm and investigate this, but the study is an excellent basis for this.”

Dr Daniel Baker, Lecturer in the Department of Psychology and senior author of the paper, said: “The high concentration of Vitamin B12 in Marmite is likely to be the primary factor behind results showing a significant reduction in participants’ responsiveness to visual stimuli.

“Since we’ve found a connection between diet and specific brain processes involving GABA, this research paves the way for further studies looking into how diet could be used as a potential route to understanding this neurotransmitter.

“Although GABA is involved in various diseases we can make no therapeutic recommendations based on these results, and individuals with a medical condition should always seek treatment from their GP.”

• Full bibliographic information‘Dietary modulation of cortical excitation and inhibition is published in the Journal of Psychopharmacology
  Anika K. Smith1, Alex R. Wade1, Kirsty E.H. Penkman2, & Daniel H. Baker
  Journal of Psychopharmacology
  http://journals.sagepub.com/toc/jop/0/0

Diminishing levels of GABA may play role in age-related cognitive decline

What protocol does your doctor have to make sure your GABA levels are OK? Is your doctor even checking your levels?
http://www.news-medical.net/news/20170117/Diminishing-levels-of-GABA-may-play-role-in-age-related-cognitive-decline.aspx

Reports new study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Diminishing levels of GABA, the primary inhibitory neurotransmitter in the brain, may play a role in cognitive decline as we age, according to a study published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. The study, led by Ronald Cohen of University of Florida's Center for Cognitive Aging and McKnight Brain Institute, shows an association between higher GABA concentrations in the frontal lobe, a brain region important for complex cognitive functioning, and superior performance on a cognitive test in healthy older adults.
The findings help researchers understand the potential role of age-related GABA decreases in cognitive decline and suggest that declining frontal GABA concentrations may help predict neurodegenerative disease.
"These results are an important step towards personalized approaches to age-related cognitive interventions," said first author Eric Porges, of the University of Florida department of clinical and health psychology in the College of Public Health and Health Professions, and a member of UF's Center for Cognitive Aging and McKnight Brain Institute.

The cause of the relationship remains unknown, and the cognitive assessment used in the study cannot pinpoint which specific cognitive domains, such as attention or memory, might be affected by declining GABA concentrations. However, the relationship suggests a potentially fruitful target for new treatments.
"Interventions that increase GABA levels (such as exercise) could potentially offset these changes, and this paper opens up a pathway for investigating this exciting possibility," said Cameron Carter, Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.
Ninety-four healthy older adults (average age of 73 years) who participated in the study completed the Montreal Cognitive Assessment, which probes several domains of cognition. Porges and colleagues also measured GABA concentrations in the frontal and posterior cortices of each participant to target regions that are important for high level cognitive functioning.
The analysis supports previously reported GABA reductions during healthy adulthood and revealed that GABA concentrations continue to diminish in both regions into advanced age. The analysis also revealed an association between reduced GABA concentrations in the frontal lobe and poor test scores. This relationship existed even after controlling for age-related changes in cognitive function and tissue atrophy.
"To find that, independent of age and tissue atrophy, GABA levels predict individual differences in cognitive outcome is a provocative finding that may provide insight into physiological mechanisms of age-related cognitive decline," said Porges.
The relationship between GABA concentration and MoCA score was not found in the posterior region, indicating the effect on cognition is specific to reductions in the frontal lobe rather than brain-wide changes in GABA concentrations.

Source:

Elsevier

More GABA in One Brain Region Linked to Better Working Memory

What is your doctor doing to make sure that you have enough GABA in that area? A stroke protocol? Bet your doctor is doing nothing and knows nothing about this.
http://neurosciencenews.com/dpfc-gaba-working-memory-5529/
ummary: Researchers report the amount of GABA in person’s dorsolateral prefrontal cortex is linked the ability to keep several things in mind simultaneously.
Source: Stanford.
The amount of a particular chemical in a particular part of your brain predicts your ability to simultaneously hang onto several bits of information in your working memory, a Stanford University School of Medicine scientist and his University of California-Davis collaborators have learned.
The discovery helps to clarify at least one aspect of the brain’s mysterious ways, and could someday help guide therapies for those whose working memory could stand improvement.
And whose couldn’t?
Working memory is the brain function that lets you carry on a phone conversation while adding three numbers in your head and remembering that you need to steer the car onto the freeway exit in about two minutes — all this time not forgetting who you’re talking to. Like a computer’s RAM, working memory serves as a buffer where information, derived from the senses or retrieved from long-term memory, can be temporarily placed so the conscious brain can process it. It’s tied to assessments of cognitive capacity such as IQ, and to real-world outcomes such as academic performance.
Load, maintenance, distraction resistance
As most people eventually find out, working memory declines with age.
“Deficits in working memory also characterize various neuropsychiatric conditions and are particularly evident in schizophrenia,” said Jong Yoon, MD, an assistant professor of psychiatry and behavioral sciences at Stanford and a psychiatrist at the Palo Alto Veterans Affairs Health Care System who sees numerous patients with this disorder.
Yoon is the lead author of a study that will be published Nov. 16 in the Journal of Neuroscience. The study teases apart three key components of working memory and shows that one component, but not the other two, is tied to the amount of a chemical called GABA in a brain area known as the dorsolateral prefrontal cortex, or DLPFC. Richard Maddock, MD, a professor of psychiatry at UCD, is senior author of the study.
This component, referred to as load, is a measure of the number of separate bits of information a person’s working memory can store at the same time. A second component, maintenance, denotes how long information can be stored in working memory before it’s lost. A third, distraction resistance, gauges how well an individual’s working memory holds onto information in the face of interfering stimuli.
The DLPFC, a broad swath of neural tissue on the forebrain surface, has been shown in animal studies and in observations of brain-damaged patients to be integral to high-level executive functions in the brain, such as planning, prioritizing and avoiding distractions. It has likewise been strongly implicated in working memory. The DLPFC orchestrates activity in numerous distant centers throughout the brain, including the visual cortex, which is located near the brain’s surface but in the hindbrain.

GABA tied to working-memory capacity
“No previous study has ever pinpointed GABA’s link with working memory in humans,” said Yoon. “Working memory is a complex process, requiring coordinated activity in centers throughout the brain. Yet, remarkably, the amount of this one chemical in a single part of the brain accounts for close to one-third of the variance in individuals’ load capacity.”
In the study, 23 healthy participants ages 19-32 were subjected to batteries of tests of working memory. Yoon reasoned that different components of working memory would involve different neurotransmitter inputs. So he devised working-memory tests that separated the measurement of load, maintenance and distraction resistance.

The study teases apart three key components of working memory and shows that one component, but not the other two, is tied to the amount of a chemical called GABA in a brain area known as the dorsolateral prefrontal cortex, or DLPFC. NeuroscienceNews.com image is for illustrative purposes only.

Participants repeated several related tasks. In the simplest, they were shown a drawing of a face and then, after a two-second delay, shown a second face and asked whether it was the same as or different from the first one. Variations of this task — initially presenting two faces instead of just one; lengthening the intervening delay; or displaying a different, irrelevant face between the initial and final displays — tested load, maintenance and distraction resistance, respectively. The investigators compared individuals’ error rates on the simple version of the task with outcomes on tasks taxing one or another working-memory component more heavily. The smaller the deterioration in performance on a test of a particular working-memory component, the greater the individual’s capacity regarding that component was judged to be.
Stop and go signals
Using an advanced imaging method, the scientists measured GABA levels in the DLPFC and, for comparison, in the visual cortex. GABA, secreted by nerve cells, is an inhibitory neurotransmitter: Its uptake by other nerve cells inhibits their firing.
Yoon and his associates also measured levels of an excitatory neurotransmitter, glutamate. By far the two most abundant neurotransmitters in the brain, GABA and glutamate are considered to be that organ’s stop and go signals.
Individuals with higher levels of GABA in their DLPFC performed better on tests of their load capacity — the ability to juggle more bits of information — the researchers found. In contrast, no significant association emerged linking GABA levels in the DLPFC to maintenance or to distraction resistance, or tying participants’ load capacity to GABA levels in the visual cortex. Nor did imaging reveal any connection between performance on tests of load capacity and levels of glutamate in the DLPFC.
Schizophrenic patients, Yoon said, are known to be deficient in an enzyme essential to GABA production. So, drugs that boost GABA levels or function in the brain might prove helpful in restoring their impaired working memory. He plans to test this hypothesis.
The work is an example of Stanford Medicine’s focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.

About this neuroscience research article

Funding: The study was funded by the National Institute for Mental Health (grant R21NH090475).
Stanford’s Department of Psychiatry and Behavioral Sciences also supported the work.
Source: Bruce Goldman – Stanford
Image Source: This NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Dorsolateral Prefrontal Cortex GABA Concentration in Humans Predicts Working Memory Load Processing Capacity” by Jong H. Yoon, Anthony Grandelis and Richard J. Maddock in Journal of Neuroscience. Published online November 16 2016 doi:10.1523/JNEUROSCI.1970-16.2016

Yoga: More Effective than Walking to Boost Anti-Anxiety Neurotransmitter

And you have a lot of anxiety since your doctor has no clue how to get you 100% recovered.
https://draxe.com/how-yoga-changes-your-brain/
Did you ever wonder how yoga changes your brain? As it turns out, that post-session happiness you feel isn’t just in your head. Using brain scans, scientists can now prove that yoga actually changes your brain chemistry. And that’s a good thing. Just like practicing tai chi moves, using yoga as a form of exercise and meditation can help naturally treat a range of health issues, particularly ones rooted in the brain.

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How Yoga Changes Your Brain

While natural therapies, including yoga, don’t have a ton of funding for major studies compared to the pharmaceutical and biotech industries, we are starting to see some compelling science emerge. Some of the best science to date showing how yoga changes your brain involves yoga’s impact on anxiety, depression and pain tolerance.
Yoga Unleashes GABA
Did you know yoga is a natural remedy for anxiety? That’s because yoga impacts our brain’s GABA levels. GABA is short for gamma-aminobutryic acid, sometimes referred to as your body’s “chill out” neurotransmitter. GABA is crucial for suppressing neural activity. Your GABA neurotransmitters produce a calming effect similar to of drinking alcohol (without the harmful side effects). And, of course, alcohol’s calming effects are only temporary, with anxiety often rising once the buzz wears off. (1, 2)
Yoga bumps up your brain’s natural GABA production without traditional anti-anxiety drugs designed to help your body release GABA. (Getting off of these benzodiazepine drugs can lead to serious withdrawal symptoms.) Yoga sounds much better than insomnia, seizures and, ironically, more anxiety linked with drug withdrawal. (3)
Bring on the asanas! And get this. While walking to lose weight really works, it may not be your best defense against anxiety. Practicing yoga unleashes more anxiety-quelling GABA in the brain’s thalamus than walking, according to a 2010 study published in the Journal of Alternative and Complementary Medicine. Compared to pleasure reading for an hour, a 60-minute yoga session increases GABA levels by 27 percent. (4) Because of its combination of breathing, meditation and movement, yoga could be one of the best exercises to combat anxiety.

Some good posters at the link.

Sleep apnea takes a toll on brain function

How fucking long is it going to take before this is tested for and treated in all stroke patients? Stroke protocol anyone? I'll say 50 years. I got the finger pulse oximetry test which obviously did not identify my sleep apnea.
https://www.uclahealth.org/news/sleep-apnea-takes-a-toll-on-brain-function
One in 15 adults has moderate to severe obstructive sleep apnea, a disorder in which a person’s breathing is frequently interrupted during sleep — as many as 30 times per hour.
People with sleep apnea also often report problems with thinking such as poor concentration, difficulty with memory and decision-making, depression, and stress.
According to new research from the UCLA School of Nursing,  published online in the Journal of Sleep Research,  people with sleep apnea show significant changes in the levels of two important brain chemicals, which could be a reason that many have symptoms that impact their day-to-day lives.
UCLA researchers looked at levels of these neurotransmitters — glutamate and gamma-aminobutyric acid, known as GABA — in a brain region called the insula, which integrates signals from higher brain regions to regulate emotion, thinking and physical functions such as blood pressure and perspiration. They found that people with sleep apnea had decreased levels of GABA and unusually high levels of glutamate.
GABA is a chemical messenger that acts as an inhibitor in the brain, which can slow things down and help to keep people calm — like a brake pedal. GABA affects mood and helps make endorphins.

UCLA

Paul Macey

Glutamate, by contrast, is like an accelerator; when glutamate levels are high, the brain is working in a state of stress, and consequently doesn’t function as effectively. High levels of glutamate can also be toxic to nerves and neurons.
“In previous studies, we’ve seen structural changes in the brain due to sleep apnea, but in this study we actually found substantial differences in these two chemicals that influence how the brain is working,” said Paul Macey, the lead researcher on the study and an associate professor at the UCLA School of Nursing.
Macey said the researchers were taken aback by the differences in the GABA and glutamate levels.
 “It is rare to have this size of difference in biological measures,” Macey said. “We expected an increase in the glutamate, because it is a chemical that causes damage in high doses and we have already seen brain damage from sleep apnea. What we were surprised to see was the drop in GABA. That made us realize that there must be a reorganization of how the brain is working.”
Macey says the study’s results are, in a way, encouraging. “In contrast with damage, if something is working differently, we can potentially fix it.”
The link between sleep apnea and changes in the state of the brain is important news for clinicians, Macey said.
“What comes with sleep apnea are these changes in the brain, so in addition to prescribing continuous positive airway pressure, or CPAP — a machine used to help an individual sleep easier, which is the gold standard treatment for sleep disturbance — physicians now know to pay attention to helping their patients who have these other symptoms,” Macey said. “Stress, concentration, memory loss — these are the things people want fixed.”
In future studies, the researchers hope to determine whether treating the sleep apnea — using CPAP or other methods — returns patients’ brain chemicals back to normal levels. If not, they will turn to the question of what treatments could be more effective. They are also studying the impacts of mindfulness exercises to see if they can reduce glutamate levels by calming the brain.
The study was conducted at the UCLA Sleep Disorder Center. The other researchers on the study were Manoj Sarma, Rajakumar Nagarajan, Ravi Aysola, Jerome Siegel, Ronald Harper and M. Albert Thomas, all of UCLA.
The research was funded by a grant from the National Institute of Nursing Research.

NOOTROPICS IN COMPLEX THERAPY OF CHRONIC CEREBRAL ISCHEMIA

With 13 pages and 58 references in here this is too much for a stroke-addled non-medical person like myself to have any understanding of how to apply this to survivors. So either you are going to have to become a genius or you wait 200 years before this is translated into stroke protocols. Your choice. Your doctor has already had two years to figure this out and I bet has done absolutely nothing.

NOOTROPICS IN COMPLEX THERAPY OF CHRONIC CEREBRAL ISCHEMIA

No longer available, so you'll have to ask your doctor to find it. If your doctor is any good at all they will have it in their stroke references
If your doctors aren't salivating over having all these possibilities laid out for them to help survivors you have idiots for doctors. This should in any reasonable world trigger dozens of clinical trials. But it won't because SOMEONE ELSE WILL SOLVE THOSE FUCKING PROBLEMS.
But not in your lifetime.

CLASSIFICATION OF NOOTROPICS

In clinical practice, these drugs are classified

into two major groups: nootropics of direct ac-

tion (cognitive enhancers) and neuroprotective

agents [31, 32]:

I. Cognitive enhancers or «true» nootropics:

1. Pyrrolidone nootropics(racetams) with pre-

dominant metabolite action: Piracetam, Fenotro-

pil combined racetams (Thiocetam, Olatropil, and

Phezam).

2. Cholinergic agents: enhancers of synthesis and

release of acetylcholine (Phosphatidylserine, leci-

thin, Citicoline); cholinergic receptor agonists (Oxo-

tremorine, Bethanechol); and acetylcholi nes terase

inhibitors (Physostigmine, Galantha mine, etc.)

3. Neuropeptides and neurotrophic cerebroprotec-

tors: Semax, Cerebrolysin, Cortexin, Cerebrocu rin.

4. Modulators of glutamatergic system:

a) low-affinity NMDA receptor polyamine site antago-

nists and partial agonists of AMPA receptors: Me-

mantine, Ademol);

b) AMPA receptor agonists: Nooglutyl;

c) AMPA receptor partial agonists, as well as en-

hancers of noradrenaline and dopamine release:

(Ritalin, Donepezil);

d) NMDA receptor co-agonists: glycine;

e) NMDA mimetics: glutamic acid, D-cycloserine.

5. Dopamine receptor agonists: Pronoran;

6. GABA receptor agonists: Baclofen.

II. Neuroprotective agents:

1. Activators of brain metabolism: Mildronat,

Phosphatidylserine, xanthine derivatives of Pen-

toxifylline, etc.

2. Cerebral vasodilators: Vincamine, Vinpocet-

ine, Nicergoline, etc.

3. Calcium channel blockers: Nimodipine, Cin-

narizine, Flunarizine, etc.

4. Antioxidants: Mexidol, a-tocopheryl acetate,

Thiotriazoline, Emoxipin, Cytoflavin, Glutoxim.

5. Substances affecting the GABA system

: Ami-nalon (Gammalon), Pathogen, Picamilon, Fenib-

ut (Noofen), sodium hydroxybutyrate.

6. Different groups of substances: orotic acid,

Naftidrofuryl, ginseng, lemongrass, Ginkgo bi lo-

ba, and Siberian ginseng.

For the direct nootropics the effect on memory

is the main action, although they have other phar-

macological properties (anticonvulsant, antihy-

poxic, circulatory, antioxidant, etc.) as well. The

direct nootropics include substances with very

different structure, from the relatively simple ra-

cetams to the complex peptide formations. The

neuroprotective agents comprise brain metabo-

lism activators, cerebral vasodilators, calcium an-

tagonists, antioxidants, and substances affecting

GABA system.