Limbic Perfusion Is Reduced in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

[SWAlexander]

excerpt:
The differences in the rCBF between the ME/CSF patients and healthy controls were statistically assessed with voxel-wise and AAL ROI-based two-sample t-tests. Linear regression analysis was also performed on the rCBF data by using the symptom severity score as the main regressor. In comparison with the healthy controls, the patient group showed significant hypoperfusion (uncorrected voxel wise p ≤ 0.001, FWE p ≤ 0.01) in several brain regions of the limbic system, including the anterior cingulate cortex, putamen, pallidum, and anterior ventral insular area. For the ME/CFS patients, the overall symptom severity score at rest was significantly associated with a reduced rCBF in the anterior cingulate cortex. The results of this study show that brain blood flow abnormalities in the limbic system may contribute to ME/CFS pathogenesis. View Full-Text
https://www.mdpi.com/2379-139X/7/4/56

 

[pattismith]

interestingly the Anterior Cingulate Cortex (ACC) dysfunction in ADHD is very often cited.

I suspect the "attention deficit" described in this trouble is very similar to the "brain fog" ME/CFS patients experiment and talk about.

The entire cingulate cortex is engaged in the structure/function abnormalities found in attention-deficit/hyperactivity disorder (ADHD).

In ADHD, which is the most common developmental disease, impaired impulse control and cognition often trace to anterior midcingulate cortex (aMCC) in Go/No-go tests, decoding and reading, the Stroop Color and Word Test, and the Wisconsin Card Sorting Test (WCST), with volume deficits in anterior cingulate cortex (ACC) and posterior midcingulate cortex (pMCC).
Students struggle in class due to malfunctioning aMCC, pregenual anterior cingulate cortex (pACC), and dorsal posterior cingulate cortex (dPCC), and to core deficits in response/task switching in aMCC.....

Cingulate impairments in ADHD: Comorbidities, connections, and treatment - PubMed (nih.gov)

 

[pattismith]

The anterior cingulate cortex is also involved in Parkinson patients

Once a diagnosis of Parkinson's disease (PD) has been made, even in its earliest prodromal form of subjective memory impairment, cognitive impairment has begun and involves anterior cingulate cortex (ACC).
...
Voxel-based morphometry has been used in many studies of mild cognitive impairment (MCI) in PD to show reduced thickness in ACC and posterior cingulate cortex (PCC). Regional cerebral blood flow is altered in association with verbal IQ in all the PCC and anterior midcingulate cortex and executive impairments in ACC.

Amnestic MCI is associated with reduced dopamine-2 receptor binding in ACC and, even in cognitively normal PD cases, dopaminergic pathways in ACC are impaired early in association with executive and language functions. The cholinergic system also has substantial changes in nicotinic and muscarinic receptor binding, and therapy with donepezil improves Mini-Mental State Exam scores and metabolism in pACC and dPCC. Cingulate cortex is also engaged in two critical symptoms: apathy and visual hallucinations.

Cingulate cortex in Parkinson's disease - PubMed (nih.gov)

 

[pattismith]

Long COVID: cognitive complaints (brain fog) and dysfunction of the cingulate cortex | SpringerLink

Published: 18 June 2021

 

[SWAlexander]

pattismith: I wonder if ME/CFS brain fog is related to "white matter" that is found in the deeper tissues of the brain (subcortical)? It contains nerve fibers (axons), which are extensions of nerve cells (neurons). Many of these nerve fibers are surrounded by a type of sheath or covering called myelin. Myelin gives the white matter its color.

 

[SWAlexander]

Long COVID: cognitive complaints (brain fog) and dysfunction of the cingulate cortex | SpringerLink

Published: 18 June 2021

I truly wonder what the future looks like 5 years post COVID or even the next generatiion.

 

[pattismith]

pattismith: I wonder if ME/CFS brain fog is related to "white matter" that is found in the deeper tissues of the brain (subcortical)? It contains nerve fibers (axons), which are extensions of nerve cells (neurons). Many of these nerve fibers are surrounded by a type of sheath or covering called myelin. Myelin gives the white matter its color.

this question would need more investigation

 

[Violeta]

Bacopa monnieri is good for increasing circulation to the brain. It's known to be good for Parkinson's.

https://pubmed.ncbi.nlm.nih.gov/23772955/

 

[pattismith]

In GWI too the ACC is altered,

It's confirmed in this 2021 study

Association of the tissue microstructural diffusivity and translocator protein PET in Gulf War Illness - ScienceDirect

Our study is the first to provide evidence of a relationship between PET and dMRI modalities in GWI and suggests that microstructural changes in the ACC and MCC are correlated to mood symptoms and cognitive performances in GWI veterans.

 

[Violeta]

This is very important information.
In the case of GWI veterans, neuroinflammation seems to be the main cause.

"our group observed widespread cortical elevations in neuroinflammation. Elevated [11C]PBR28 signal was evident in regions including the anterior and midcingulate cortices (ACC and MCC, respectively), in GWI veterans compared to healthy controls or healthy GW veterans (Alshelh et al., 2020). These abnormal neuro-immune responses appear to trigger downstream macro- and microstructural changes in the brain (Koo et al., 2018). Indeed, diffusion magnetic resonance imaging (dMRI) studies found that microstructural alterations (including the ACC) were associated with elevated levels of peripheral proinflammatory cytokines, and with worse fatigue symptoms, in GWI veterans"

 

[Pyrrhus]

Thanks for posting this, @SWAlexander!

Here's the full abstract of this (Li et al., 2021) paper:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an illness characterized by a diverse range of debilitating symptoms including autonomic, immunologic, and cognitive dysfunction. Although neurological and cognitive aberrations have been consistently reported, relatively little is known regarding the regional cerebral blood flow (rCBF) in ME/CFS.

In this study, we studied a cohort of 31 ME/CSF patients (average age: 42.8 ± 13.5 years) and 48 healthy controls (average age: 42.9 ± 12.0 years) using the pseudo-continuous arterial spin labeling (PCASL) technique on a whole-body clinical 3T MRI scanner. Besides routine clinical MRI, the protocol included a session of over 8 min-long rCBF measurement.

The differences in the rCBF between the ME/CSF patients and healthy controls were statistically assessed with voxel-wise and AAL ROI-based two-sample t-tests. Linear regression analysis was also performed on the rCBF data by using the symptom severity score as the main regressor.

In comparison with the healthy controls, the patient group showed significant hypoperfusion (uncorrected voxel wise p ≤ 0.001, FWE p ≤ 0.01) in several brain regions of the limbic system, including the anterior cingulate cortex, putamen, pallidum, and anterior ventral insular area. For the ME/CFS patients, the overall symptom severity score at rest was significantly associated with a reduced rCBF in the anterior cingulate cortex. The results of this study show that brain blood flow abnormalities in the limbic system may contribute to ME/CFS pathogenesis.

 

[Martin aka paused||M.E.]

Many of these nerve fibers are surrounded by a type of sheath or covering called myelin.

A dysfunctional myelin sheath would lead to inefficient transmission of electrical impulses (no saltatory conduction). Could explain brain fog. Theoretically…

 

[SWAlexander]

A dysfunctional myelin sheath would lead to inefficient transmission of electrical impulses (no saltatory conduction). Could explain brain fog. Theoretically…

"A dysfunctional myelin sheath would lead to inefficient transmission of electrical impulses" I´m glad you mention the myelin sheath. Here are some details: https://www.khanacademy.org/science...nervous-system/v/saltatory-conduction-neurons.
White matter can only be found by MRI with contrast. Unfortunately, not many people with brain fog will get an MRI even though dysfunctional myelin sheaths can lead to many other neurotransmitters problems.

 

[Violeta]

I guess we will have to be the ones to figure out what is causing it and how to remedy it.

Suggestions:

ammonia
aldehyde
for example, the cingulate gyms, severely hypoperfused when hypotension complicates .....

 

[pattismith]

another interesting study about Anterior Cingulate Cortex dysfunction (in ADHD and SLEEP DEPRIVATION)

A coordinate-based meta-analysis comparing brain activation between attention deficit hyperactivity disorder and total sleep deprivation

Jared M Saletin, Stephanie Jackvony, Katherina A Rodriguez, Daniel P Dickstein
Sleep, Volume 42, Issue 3, March 2019, zsy251, https://doi.org/10.1093/sleep/zsy251
Published:

12 December 2018

https://forums.phoenixrising.me/javascript:;
Abstract

Study Objectives

Sleep disruption is common in attention deficit hyperactivity disorder (ADHD). Likewise, deficits in attention are a hallmark of sleep deprivation in healthy individuals. Whether ADHD and sleep deprivation modulate common, or disparate, neural systems is unknown. ....

Results

Conjunction analyses revealed overlapping hypoactivations between ADHD and sleep loss in executive function regions, notably the dorsal anterior cingulate cortex.

Sleep deprivation, however, was associated with significantly exaggerated hyperactivation in the thalamus.

Conclusions

Our study indicates that ADHD and sleep deprivation share a common neural signature:

hypoactivation of executive function neuroanatomy.

In contrast, sleep loss, but not ADHD, was associated with thalamic hyperactivations, intimating a potential compensatory response in sleep loss not present in ADHD.

By elucidating shared and distinct patterns of functional neuroanatomy, these data provide novel targets for future experimental investigations of sleep loss in ADHD.

 

[pattismith]

Thanks for posting this, @SWAlexander!

Here's the full abstract of this (Li et al., 2021) paper:

Strangely, if we look back to older brain perfusion studies, the most common abnormality found was brainstem hypoperfusion.

One drug known to improve brainstem blood flow is Betahistine, it is cheap and with a good safety profile.

It is a drug for vertigo that improves perfusion of vestibular and cochlear nucleus in the brainstem.

three weeks headache fixed with betahistine | Phoenix Rising ME/CFS Forums

Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review | Journal of Translational Medicine | Full Text (biomedcentral.com)

 

[pattismith]

Long COVID: cognitive complaints (brain fog) and dysfunction of the cingulate cortex | SpringerLink
2022

Many patients who have suffered from acute COVID infections have long-lasting symptoms affecting several organs including the brain.

This long COVID status can include “brain fog” and cognitive deficits that can disturb activities of daily living and can delay complete recovery. Here, we report two cases of neurological long COVID with abnormal FDG PET findings marked by hypometabolic regions of the cingulate cortex.