Department name (edit in View > Header and

Footer...) Department name (edit in View > Header and Footer...)National Centre for Neuroimmunology and Emerging Diseases

Brain stem myelination

and

MRI changes in CFS/ME

Leighton BARNDEN

National Centre for Neuroimmunolgy and Emerging Diseases

Griffith Uni, Gold Coast, QLD

• Brain stem • myelination • MRI studies of CFS/ME• Results• Conclusions

Brain stem myelination and

MRI changes in CFS/ME

brain stem midbrainponsmedulla

Brain stem

where is it?

Brain stem

Multiple nuclei send fibres to the cortex where they release excitatory neuro-hormones.

This process maintains arousal and consciousness

- cognitive performance- initiation of movement

There are also inhibitory fibres that regulate the transition to sleep and the duration/intensity of pain.

Other nuclei regulateheart rate, blood pressure

also

temperature, breathing,gut & immune function … and more (autonomic).

Brain stem stress

cuneiform nucleus

vasomotor centre

to blood-pressure,heart-rate effectors

thalamus

hypothalamus

midbrain

pons

medulla

• If transmission of signals within the brain stem is impairedit may adversely affect:

arousal, cognitive performance, initiation of movement, quality of sleep, pain & bodily functions

Brain stem

Myelination

speeds up signal transmission

90% of T1 MRI contrast in WM derives from myelinStuber et al 2014 Neuroimage 93, 95

nerve fibre

Voxel-based statistics

StatisticalParametricMap

(T statistic)

Study designs

Normal controls

Compare groups

CFS group

MR image

Voxel-based statistics

Test for linear regression

MR images and clinical score

CFS group

T statistic

Study Design

Normal controls

The relationship between MRI and blood pressure

Is it different in CFS? If so, where?

• In RED normal variation in NC yields MRI – BP relationship.• relationship is abnormal in CFS• ? communication between regulatory nuclei in brainstem.

T1wSE vs PP

CnF of RAS

CnFCnF

VTA

T2wSE vs PP

WM vol vs diasBP

Barnden L, Neuroimage Clinical 2016

stress

Myelin vs CFS Severitymore severe CFS/ME -> more myelin

Barnden et al 2015NMR Biomed, 28, 404

Comparison of myelin in CFS vs HC (healthy controls)plot, for individuals,

sensorimotor vs brainstem

Brainstemvs

SensorimotorMyelin

Inverse relationship

Sensorimotor upregulated

to compensatefor weak brainstem

nerve signals

brainstem

sensori-motor

Barnden L, Neuroimage Clinical 2018

Brainstem connectivity is impaired in CFS/ME

P = 0.0002

fMRI can detect altered signal transmission (connectivity)within the brainstem

Brain stem differences in CFS/ME - other reports

- Reduced perfusion via SPECT (not reproduced)Costa, QJ Med, 1995

- Inflammation via PET (9 subjects)Nakatomi, J Nucl Med, 2014

- White Matter volume reduction via MRI (inconsistent)Finkelmeyer, Neuroimage Clinical, 2018

Barnden 2011NMR Biomed

- Conclusions -in CFS/ME

• Autonomic regressions with MRI imply impaired communication between brainstem nuclei.

• Severity-dependent upregulated myelin in frontal WM implies weakened nerve signals from the brainstem.

• A compensatory brainstem - sensorimotor myelin relationship implies upregulated sensorimotor myelin is a response to impaired brainstem nerve conduction.

• Functional MRI confirms reduced connectivity between the brainstem medulla and midbrain.

• This will affect multiple regulatory functions and may explain many symptoms of CFS/ME.

• What causes damage to the brainstem?

thank you

Barnden L, NMR Biomed 2015

MRI variation is associated with Depression, But independent of MRI variation associated with severity

Depressionadjusted

Myelinvs

CFS Severity

What is the role of Anxiety and Depression in CFS/ME?