The overall objective of this study is to combine a conceptual model with empirical evidence to demonstrate that the start of a migraine attack corresponds to a critical transition that occurs when the dynamical brain system approaches a tipping…
ID
Source
Brief title
Condition
- Headaches
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
AC-EEG: For the AC-EEG recordings we will use eight to 128 leads, which we will
use to measure fluctuations. Our interpretation is that changes in fluctuations
will become slower, resulting in e.g. increased autocorrelation and variance.
Phase and amplitude correlations between electrodes will be used as measure of
cortical excitability.
VEP: Visual evoked potentials (VEPs) are electrical potential differences
recorded from the scalp in response to visual stimuli. They represent a mass
response of cortical and possibly subcortical visual areas. In this study we
will use unpatterned flash stimuli because this is a simple and robust way of
visual stimulation that will perturb the visual system. We aim to measure the
dynamics from the VEP responses (e.g. timing, amplitude of frequency) to assess
the recovery phase of the visual system after perturbation to its original
state. We expect that the time the visual system needs to recover to its
original state is a measure of resilience of the system.
Secondary outcome
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Background summary
Self-propagating, centrifugally-expanding waves of cerebral neuronal firing,
known as spreading depolarizations (SD), are believed to be the starting point
of attacks of migraine. We hypothesize that the start of a SD corresponds to a
critical transition that occurs when the dynamical brain system approaches a
tipping point. Migraine may thus strike when a combination of genetic
predisposition and modulating factors such as hormonal fluctuations and other
endogenous and exogenous changes have raised the neuronal excitability to a
level where even minor perturbations can trigger spreading depolarization. As
the vicinity of a tipping point is associated with the universal phenomenon of
*critical slowing down* in dynamical systems, we expect that, in the brain,
this phenomenon will be reflected in electrophysiological characteristics which
may serve as early warning signals to impending migraine attack. Identifying
such a new class of early warning signals may open up new avenues for
dissecting triggering mechanisms of migraine attacks and developing measures to
prevent impending attacks.
Study objective
The overall objective of this study is to combine a conceptual model with
empirical evidence to demonstrate that the start of a migraine attack
corresponds to a critical transition that occurs when the dynamical brain
system approaches a tipping point.
1. To develop an experimental paradigm to objectively measure parameters
indicating the approach of a critical transition as a landmark in the dynamic
alterations in brain excitability and thereby predict the tipping point in
migraine patients.
2. To show that this experimental paradigm is able to predict an impending
migraine attack in migraine patients.
Study design
Part 1: AC-EEG measurements and newly designed Visual Evoked Potential (VEP)
paradigms will be performed on volunteers for up to 6 consecutive days. Several
types of signal processing and signal analysis will be used to develop a new
experimental paradigm that enables us to measure changes in cortical
excitability. For the development of useful visual stimuli, measurements can
take place on just one occasion or on several days for repeatability and
reproducibility measures with a maximum of 6 days. Using high-density EEG the
brain topographical response to visual stimulation and functional connectivity
is studied. As part of this development stage we will also try to validate a
new questionnaire on subjective visual aversion and sensitivity which we will
also use in part 2.
Part 2: Migraine patients with a predictable component to their attacks (like
women with menstrual migraine), and a matching group of healthy controls will
come for a period of three to six measurments (maximum of 1 measurement per
day), prior to their predicted attack onset, to the department of
neurophysiology of the LUMC or at the particpant' home. Each day, they will
fill in some questionnaires, undertake pattern glare and photosensitivity
testing, and AC-EEG measurements will be done. This will take a maximum of 1
hour per day.
Study burden and risks
EEG recordings: none
LED-bril offering light flases: none
Pattern glare test: none
Photosensitivity test: increasing light intensity can cause discomfort, at that
light level the test will end.
Burden: there is no direct health gain for participating patients. Duration of
participation (max 1 hour per day with a maximum of 6 days) is moderate. After
careful consideration, we think possible side effects/risks are outweight by
the expected gain in pathophysiologic knowledge, with hopefully therapeutical
consequences in the future. In order to relieve some of the burden a fraction
of the participants will be offered to have the EEG recordings at home.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
- Migraine with/ without aura or chronic migraine according to IHS /
ICHD-III-beta criteria
- Patients have to experience active migraine, which is defined for this study
as at least one migraine attack per month on average in the past 6 months.
- Age 18 years or older
Exclusion criteria
General exclusion criteria for episodic migraine patients and healthy controls:
i) Severe depression and/or panic disorders and/or schizophrenia and/or
psychiatric disorders; ii) Epileptic disorders (epilepsy); iii) Severe visual
impairment; iv) Only for part 1: use of chronic medication (other than oral
contraceptives) in the four weeks preceding the investigation; v) Malignancy in
medical history; vi) only for part 2: use of (oral) contraceptives., Episodic
migraine patient specific: i) Only for part 1: use of prophylactic medication
for migraine in the four weeks preceding the investigation; ii) Inability to
differentiate between migraine and other variants of headache;
iii) Use of acute migraine or headache drugs on more than 6 days per month.,
Healthy control specific: i) Suffering from periodic pain attacks or a brain
disorder;
ii) Personal of family history in first-degree relatives of migraine or
trigeminal autonomic cephalgia (TAC); iii) More than one tension-type headache
in 3 months., Exclusion criteria for chronic migraine patients: i) Severe
depression and/or panic disorders and/or schizophrenia and/or psychiatric
disorders; ii) Epileptic disorders (epilepsy); iii) Severe visual impairment;
iv) Malignancy in medical history.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL47008.058.13 |