Comparison of evoked vs. spontaneous tics in a patient with trigeminal neuralgia (tic doloureux)

A 53-year old woman with tic doloureaux, affecting her right maxillary division of the trigeminal nerve (V2), could elicit shooting pains by slightly tapping her teeth when off medication. The pains, which she normally rated as > 6/10 on a visual analog scale (VAS), were electric shock-like in nature. She had no other spontaneous or ongoing background pain affecting the region. Based on her ability to elicit these tics, functional magnetic resonance imaging (fMRI) was performed while she produced brief shocks every 2 minutes on cue (evoked pain) over a 20 min period. In addition, she had 1–2 spontaneous shocks manifested between these evoked pains over the course of functional image acquisition. Increased fMRI activation for both evoked and spontaneous tics was observed throughout cortical and subcortical structures commonly observed in experimental pain studies with healthy subjects; including the primary somatosensory cortex, insula, anterior cingulate, and thalamus. Spontaneous tics produced more decrease in signals in a number of regions including the posterior cingulate cortex and amygdala, suggesting that regions known to be involved in expectation/anticipation may have been activated for the evoked, but not spontaneous, tics. In this patient there were large increases in activation observed in the frontal regions, including the anterior cingulate cortex and the basal ganglia. Spontaneous tics showed increased activation in classic aversion circuitry that may contribute to increased levels of anxiety. We believe that this is the first report of functional imaging of brain changes in tic-doloureaux

Primary Somatosensory Cortices Contain Altered Patterns of Regional Cerebral Blood Flow in the Interictal Phase of Migraine

The regulation of cerebral blood flow (CBF) is a complex integrated process that is critical for supporting healthy brain function. Studies have demonstrated a high incidence of alterations in CBF in patients suffering from migraine with and without aura during different phases of attacks. However, the CBF data collected interictally has failed to show any distinguishing features or clues as to the underlying pathophysiology of the disease. In this study we used the magnetic resonance imaging (MRI) technique—arterial spin labeling (ASL)—to non-invasively and quantitatively measure regional CBF (rCBF) in a case-controlled study of interictal migraine. We examined both the regional and global CBF differences between the groups, and found a significant increase in rCBF in the primary somatosensory cortex (S1) of migraine patients. The CBF values in S1 were positively correlated with the headache attack frequency, but were unrelated to the duration of illness or age of the patients. Additionally, 82% of patients reported skin hypersensitivity (cutaneous allodynia) during migraine, suggesting atypical processing of somatosensory stimuli. Our results demonstrate the presence of a disease-specific functional deficit in a known region of the trigemino-cortical pathway, which may be driven by adaptive or maladaptive functional plasticity. These findings may in part explain the altered sensory experiences reported between migraine attacks

Cortico–Cortical Connections of Primary Sensory Areas and Associated Symptoms in Migraine

Abstract Migraine is a recurring, episodic neurological disorder characterized by headache, nausea, vomiting, and sensory disturbances. These events are thought to arise from the activation and sensitization of neurons along the trigemino–vascular pathway. From animal studies, it is known that thalamocortical projections play an important role in the transmission of nociceptive signals from the meninges to the cortex. However, little is currently known about the potential involvement of cortico–cortical feedback projections from higher-order multisensory areas and/or feedforward projections from principle primary sensory areas or subcortical structures. In a large cohort of human migraine patients (N = 40) and matched healthy control subjects (N = 40), we used resting-state intrinsic functional connectivity to examine the cortical networks associated with the three main sensory perceptual modalities of vision, audition, and somatosensation. Specifically, we sought to explore the complexity of the sensory networks as they converge and become functionally coupled in multimodal systems. We also compared self-reported retrospective migraine symptoms in the same patients, examining the prevalence of sensory symptoms across the different phases of the migraine cycle. Our results show widespread and persistent disturbances in the perceptions of multiple sensory modalities. Consistent with this observation, we discovered that primary sensory areas maintain local functional connectivity but express impaired long-range connections to higher-order association areas (including regions of the default mode and salience network). We speculate that cortico–cortical interactions are necessary for the integration of information within and across the sensory modalities and, thus, could play an important role in the initiation of migraine and/or the development of its associated symptoms

Ictal and interictal brain activation in episodic migraine: Neural basis for extent of allodynia.

In some patients, migraine attacks are associated with symptoms of allodynia which can be localized (cephalic) or generalized (extracephalic). Using functional neuroimaging and cutaneous thermal stimulation, we aimed to investigate the differences in brain activation of patients with episodic migraine (n = 19) based on their allodynic status defined by changes between ictal and interictal pain tolerance threshold for each subject at the time of imaging. In this prospective imaging study, differences were found in brain activity between the ictal and interictal visits in the brainstem/pons, thalamus, insula, cerebellum and cingulate cortex. Significant differences were also observed in the pattern of activation along the trigeminal pathway to noxious heat stimuli in no allodynia vs. generalized allodynia in the thalamus and the trigeminal nucleus but there were no activation differences in the trigeminal ganglion. The functional magnetic resonance imaging (fMRI) findings provide direct evidence for the view that in migraine patients who are allodynic during the ictal phase of their attacks, the spinal trigeminal nucleus and posterior thalamus become hyper-responsive (sensitized)-to the extent that they mediate cephalic and extracephalic allodynia, respectively. In addition, descending analgesic systems seem as "switched off" in generalized allodynia

Increased Functional Activation of Limbic Brain Regions during Negative Emotional Processing in Migraine

Pain is both an unpleasant sensory and emotional experience. This is highly relevant in migraine where cortical hyperexcitability in response to sensory stimuli (including pain, light, and sound) has been extensively reported. However, migraine may feature a more general enhanced response to aversive stimuli rather than being sensory-specific. To this end we used functional magnetic resonance imaging to assess neural activation in migraineurs interictaly in response to emotional visual stimuli from the International Affective Picture System. Migraineurs, compared to healthy controls, demonstrated increased neural activity in response to negative emotional stimuli. Most notably in regions overlapping in their involvement in both nociceptive and emotional processing including the posterior cingulate, caudate, amygdala, and thalamus (cluster corrected, p < 0.01). In contrast, migraineurs and healthy controls displayed no and minimal differences in response to positive and neutral emotional stimuli, respectively. These findings support the notion that migraine may feature more generalized altered cerebral processing of aversive/negative stimuli, rather than exclusively to sensory stimuli. A generalized hypersensitivity to aversive stimuli may be an inherent feature of migraine, or a consequential alteration developed over the duration of the disease. This proposed cortical-limbic hypersensitivity may form an important part of the migraine pathophysiology, including psychological comorbidity, and may represent an innate sensitivity to aversive stimuli that underpins attack triggers, attack persistence and (potentially) gradual headache chronification

Comparison of evoked vs. spontaneous tics in a patient with trigeminal neuralgia (tic doloureux)

Abstract A 53-year old woman with tic doloureaux, affecting her right maxillary division of the trigeminal nerve (V2), could elicit shooting pains by slightly tapping her teeth when off medication. The pains, which she normally rated as > 6/10 on a visual analog scale (VAS), were electric shock-like in nature. She had no other spontaneous or ongoing background pain affecting the region. Based on her ability to elicit these tics, functional magnetic resonance imaging (fMRI) was performed while she produced brief shocks every 2 minutes on cue (evoked pain) over a 20 min period. In addition, she had 1–2 spontaneous shocks manifested between these evoked pains over the course of functional image acquisition. Increased fMRI activation for both evoked and spontaneous tics was observed throughout cortical and subcortical structures commonly observed in experimental pain studies with healthy subjects; including the primary somatosensory cortex, insula, anterior cingulate, and thalamus. Spontaneous tics produced more decrease in signals in a number of regions including the posterior cingulate cortex and amygdala, suggesting that regions known to be involved in expectation/anticipation may have been activated for the evoked, but not spontaneous, tics. In this patient there were large increases in activation observed in the frontal regions, including the anterior cingulate cortex and the basal ganglia. Spontaneous tics showed increased activation in classic aversion circuitry that may contribute to increased levels of anxiety. We believe that this is the first report of functional imaging of brain changes in tic-doloureaux.</p

Clinical details and migraine history.

<p>Abbreviations: Age, age in years; Sex, male (M)/female(F); Age at onset, age the headaches started in years; Frequency, number of attacks per month (median values are given in brackets); Duration, duration of illness in years; Side, dominant side of headache pain, left(L)/right(R); Allodynia, patients reporting at least one type of skin hypersensivity during migraine.</p