Sex Differences of Periaqueductal Grey Matter Functional Connectivity in Migraine

The existence of “sex phenotype” in migraine is a long-standing scientific question. Fluctuations of female sex hormones contribute to migraine attacks, and women also have enhanced brain activity during emotional processing and their functional brain networks seem to be more vulnerable to migraine-induced disruption compared to men. Periaqueductal grey matter (PAG) is a core region of pain processing and modulation networks with possible sex-related implications in migraine. In our study, sex differences of PAG functional resting-state connectivity were investigated in the interictal state in 32 episodic migraines without aura patients (16 women and 16 men). A significant main effect of sex was detected in PAG connectivity with postcentral, precentral, and inferior parietal gyri, and further differences were found between right PAG and visual areas (superior occipital gyrus, calcarine, and cuneus), supplementary motor area, and mid-cingulum connectivity. In all cases, PAG functional connectivity was stronger in female migraineurs compared to males. However, higher average pain intensity of migraine attacks correlated with stronger connectivity of PAG and middle temporal, superior occipital, and parietal gyri in male migraineurs compared to females. Migraine-related disability is also associated with PAG connectivity but without sex differences. Our results indicate that sex differences in PAG connectivity with brain regions involved in sensory and emotional aspects of pain might contribute to the “sex-phenotype” in migraine. The stronger functional connectivity between PAG and pain processing areas may be a sign of increased excitability of pain pathways even in resting-state in females compared to male migraineurs, which could contribute to female vulnerability for migraine. However, pain intensity experienced by male migraineurs correlated with increased connectivity between PAG and regions involved in the subjective experience of pain and pain-related unpleasantness. The demonstrated sex differences of PAG functional connectivity may support the notion that the female and male brain is differently affected by migraine.

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Neglected woman with hyperemesis gravidarum leading to Wernicke encephalopathy

BMJ Case Reports ◽

10.1136/bcr-2020-238545 ◽

2020 ◽

Vol 13 (12) ◽

pp. e238545

Author(s):

Papa Dasari ◽

Smitha Priyadarshini

Keyword(s):

Grey Matter ◽

Hyperemesis Gravidarum ◽

Intravenous Fluids ◽

State Of Health ◽

Wernicke Encephalopathy ◽

Periaqueductal Grey ◽

Mri Brain ◽

Good State ◽

Periaqueductal Grey Matter ◽

History Of

A teenage primigravida at 13 weeks of gestation presented with hyperemesis gravidarum of 45 days and a history of giddiness and inability to walk due to involuntary movements of limbs and eyes since 2 days. She was treated with intravenous fluids, thiamine and antiemetics. MRI brain showed hyperintensities in bilateral dorsomedial thalami, periaqueductal grey matter in T2-weighted and FLAIR images. A diagnosis of Wernicke encephalopathy was made and she was managed in intensive care unit and received injection thiamine as per the guidelines and her weakness and ataxia improved over 3 weeks and she was discharged at 17 weeks of pregnancy in good state of health.

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The effects of decerebration and destruction of nucleus raphe magnus, periaqueductal grey matter and brainstem lateral reticular formation on the depression due to surgical trauma of the jaw-opening reflex evoked by tooth-pulp stimulation in the cat

Brain Research ◽

10.1016/0006-8993(85)90592-x ◽

1985 ◽

Vol 332 (2) ◽

pp. 231-236 ◽

Cited By ~ 14

Author(s):

R.W. Clarke

Keyword(s):

Reticular Formation ◽

Grey Matter ◽

Tooth Pulp ◽

Surgical Trauma ◽

Periaqueductal Grey ◽

Nucleus Raphe Magnus ◽

Jaw Opening ◽

Raphe Magnus ◽

Periaqueductal Grey Matter ◽

Jaw Opening Reflex

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Periaqueductal grey matter stimulation produces naloxone sensitive inhibition of reticular neurones in rat caudal medulla

Life Sciences ◽

10.1016/0024-3205(82)90147-3 ◽

1982 ◽

Vol 31 (20-21) ◽

pp. 2323-2325 ◽

Cited By ~ 1

Author(s):

R.G. Hill ◽

R. Morris ◽

M.V. Sofroniew

Keyword(s):

Grey Matter ◽

Periaqueductal Grey ◽

Periaqueductal Grey Matter ◽

Caudal Medulla

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Neuronal excitability in the periaqueductal grey matter during the estrous cycle in female Wistar rats

Neuroscience ◽

10.1016/j.neuroscience.2006.08.058 ◽

2007 ◽

Vol 144 (1) ◽

pp. 325-335 ◽

Cited By ~ 32

Author(s):

K.E. Brack ◽

T.A. Lovick

Keyword(s):

Estrous Cycle ◽

Wistar Rats ◽

Grey Matter ◽

Neuronal Excitability ◽

Periaqueductal Grey ◽

Periaqueductal Grey Matter ◽

Female Wistar Rats

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Contribution of the periaqueductal grey matter to the development of hypertension in the spontaneously hypertensive rat

Journal of the Autonomic Nervous System ◽

10.1016/0165-1838(90)90189-p ◽

1990 ◽

Vol 31 (3) ◽

pp. 231-239 ◽

Cited By ~ 4

Author(s):

W.S. Redfern ◽

C.P. Yardley

Keyword(s):

Grey Matter ◽

Spontaneously Hypertensive Rat ◽

Periaqueductal Grey ◽

Spontaneously Hypertensive ◽

Hypertensive Rat ◽

Periaqueductal Grey Matter

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Resting State Functional Connectivity is Directly Related to Clinical Presentation of Mild Traumatic Brain Injury

Neurology ◽

10.1212/01.wnl.0000581088.06830.74 ◽

2019 ◽

Vol 93 (14 Supplement 1) ◽

pp. S26.2-S27

Author(s):

Teena Shetty ◽

Joseph Nguyen ◽

Esther Kim ◽

George Skulikidis ◽

Matthew Garvey ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Functional Connectivity ◽

Mild Traumatic Brain Injury ◽

Resting State ◽

Symptom Severity ◽

Grey Matter ◽

Clinical Presentation ◽

Severity Scores

ObjectiveTo determine the utility of fractional amplitude of low frequency fluctuations (fALFF) during resting state fMRI (rs-fMRI) as an advanced neuroimaging biomarker for Mild Traumatic Brain Injury (mTBI).BackgroundmTBI is defined by a constellation of functional rather than structural deficits. As a measure of functional connectivity, fALFF has been implicated in long-term outcomes post-mTBI. It is unclear however, how longitudinal changes in fALFF may relate to the clinical presentation of mTBI.Design/Methods111 patients and 32 controls (15–50 years old) were enrolled acutely after mTBI and followed with up to 4 standardized serial assessments. Patients were enrolled at either Encounter 1 (E1), within 72 hours, or Encounter 2 (E2), 5–10 days post-injury, and returned for Encounter 3 (E3) at 15–29 days and Encounter 4 (E4) at 83–97 days. Each encounter included a clinical exam, neuropsychological assessment, as well as rs-fMRI imaging. fALFF was analyzed independently in 14 functional networks and, in grey and white matter as a function of symptom severity. Symptom severity scores (SSS) ranged from 0–132 as defined by the SCAT2 symptom evaluation.ResultsIn mTBI patients, fALFF scores across 5 functional brain networks (language, sensorimotor, visuospatial, higher-order visual, and posterior salience) differed between mTBI patients with low versus high SSS (SSS <5 and >30, respectively). Overall, greater SSS were indexed by reduced connectivity (p < 0.03, Bonferroni corrected). Further analysis also identified corresponding network pairs which were most predictive of increased SSS. White matter fALFF was not correlated with symptom severity, however, decreased grey matter fALFF was significantly correlated with greater SSS (r = −0.25, p = 0.002).ConclusionsGrey matter fALFF was correlated with mTBI symptom burden suggesting that patterns of neural connectivity relate directly to the clinical presentation of mTBI. Furthermore, differences in functional network connectivity as a function of SSS may reflect which networks are implicated in recovery of mTBI.

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