Brain functional connectivity in headache disorders: A narrative review of MRI investigations

Abstract

Resting-state functional magnetic resonance imaging (rs-fMRI) is used to interrogate the functional connectivity and network organization amongst brain regions. Functional connectivity is determined by measuring the extent of synchronization in the spontaneous fluctuations of blood oxygenation level dependent (BOLD) signal. Here, we review current rs-fMRI studies in headache disorders including migraine, trigeminal autonomic cephalalgias, and medication overuse headache. We discuss (1) brain network alterations that are shared amongst the different headache disorders and (2) network abnormalities distinct to each headache disorder. In order to focus the section on migraine, the headache disorder that has been most extensively studied, we chose to include articles that interrogated functional connectivity: (i) during the attack phase; (ii) in migraine patients with aura compared to migraine patients without aura; and (iii) of regions within limbic, sensory, motor, executive and default mode networks and those which participate in multisensory integration. The results of this review show that headache disorders are associated with atypical functional connectivity of regions associated with pain processing as well as atypical functional connectivity of multiple core resting state networks such as the salience, sensorimotor, executive, attention, limbic, visual, and default mode networks.

Keywords: Functional connectivity; magnetic resonance imaging; medication-overuse headache; migraine; trigeminal autonomic cephalalgias.

Figures

Figure 1.

Flowchart for literature search. *Articles were selected for inclusion based on author discussion, originality and contribution to the topic of “brain functional connectivity.”

Figure 2.

A schematic illustration of regions and functional networks (default mode, salience, sensory) where studies have shown altered functional connectivity in migraine patients during attacks compared to between attacks. Important regions of functional networks that are altered in migraineurs during the attack compared to between attacks include the following: Default mode network regions: medial prefrontal cortex (mPFC) and anterior cingulate cortex (aCC), precuneus and posterior cingulate cortex (pCC). Salience network regions: insula and (dorsal) anterior cingulate. Sensory network region: somatosensory cortex (SS). Migraineurs during the attack have stronger functional connectivity between the pons and the somatosensory cortex (SS).

Figure 3.

Interictal migraine patients with aura compared to interictal migraine patients without aura have stronger functional connectivity within visual cortex regions (VC) including the lingual gyrus (LG) and stronger functional connectivity of occipital regions with the anterior insula. Migraineurs with aura have higher amplitudes of resting-state fluctuations in frontal areas, cingulate cortex (CC), inferior parietal lobule (iPL) and the cerebellum.

Figure 4.

A schematic illustration of regions and functional networks (default mode, salience, sensory, and attention) where studies have shown altered functional connectivity in patients with cluster headache compared to healthy controls. In cluster headache, the hypothalamus has shown abnormal functional connectivity to regions of the default mode, salience, sensory and attention networks. Important regions of functional networks that are altered in cluster headache include the following: Default mode network regions: medial prefrontal cortex (mPFC) and anterior cingulate cortex (aCC), precuneus and posterior cingulate cortex (pCC) and the inferior parietal cortex (iPC). Salience network regions: insula and (dorsal) anterior cingulate. Sensory network region: somatosensory cortex (SS). Attention network regions: inferior frontal (iF) and middle frontal (mF) cortex, and the temporo-parietal junction (TPJ) and occipital cortex (OCC).

Figure 5.

Regions of the pain reward system where patients with medication-overuse headache show altered functional connectivity including the nucleus accumbens, putamen, caudate, hippocampus, periaqueductal gray (PAG), precuneus and the insula.