Headache Related Alterations of Visual Processing in Migraine Patients.

peer reviewedMigraine is characterized by an increased sensitivity to visual stimuli that worsens during attacks. Recent evidence has shown that feedforward volleys carrying incoming visual information induce high-frequency (gamma) oscillations in the visual cortex, while feedback volleys arriving from higher order brain areas induce oscillatory activity at lower frequencies (theta/alpha/low beta). We investigated visually induced high (feedforward) and low (feedback) frequency activations in healthy subjects and various migraine patients. Visual evoked potentials from 20 healthy controls and 70 migraine patients (30 interictal and 20 ictal episodic migraineurs, 20 chronic migraineurs) were analyzed in the frequency domain. We compared power in the theta-alpha-low beta and gamma range between groups, and searched for correlations between the low-to-high frequency activity ratio and number of monthly headache and migraine days. Compared to healthy controls, interictal migraine patients had increased visually induced low frequency (feedback) activity. Conversely, ictal and chronic migraine patients showed an augmented gamma band (feedforward) power. The low-frequency-to-gamma (feedback/feedforward) activity ratio correlated negatively with monthly headache days and tended to do so with migraine days. Our findings show that visual processing is differentially altered depending on migraine cycle and type. Feedback control from higher order cortical areas predominates interictally in episodic migraine while migraine attacks and chronic migraine are associated with enhanced incoming afferent activity, confirming their similar electrophysiological profile. The presence of headache is associated with proportionally higher gamma (feedforward) activities. PERSPECTIVE: This study provides an insight into the pathophysiology of migraine headache from the perspective of cortical sensory processing dynamics. Patients with migraine present alterations in feedback and feedforward visual signaling that differ with the presence of headache

The network model of depression as a basis for new therapeutic strategies for treating major depressive disorder in Parkinson’s disease

The high prevalence of major depressive disorder in people with Parkinson's disease, its negative impact on health-related quality of life and the low response rate to conventional pharmacological therapies call to seek innovative treatments. Here, we review the new approaches for treating major depressive disorder in patients with Parkinson's disease within the framework of the network model of depression. According to this model, major depressive disorder reflects maladaptive neuronal plasticity. Non-invasive brain stimulation using high frequency repetitive transcranial magnetic stimulation over the prefrontal cortex has been proposed as a feasible and effective strategy with minimal risk. The neurobiological basis of its therapeutic effect may involve neuroplastic modifications in limbic and cognitive networks. However, the way this networks reorganize might be strongly influenced by the environment. To address this issue, we propose a combined strategy that includes non-invasive brain stimulation together with cognitive and behavioral interventions

Brain mechanisms underlying automatic and unconscious control of motor action

Are we in command of our motor acts? The popular belief holds that our conscious decisions are the direct causes of our actions. However, overwhelming evidence from neurosciences demonstrates that our actions are instead largely driven by brain processes that unfold outside of our consciousness. To study these brain processes, scientists have used a range of different functional brain imaging techniques and experimental protocols, such as subliminal priming. Here, we review recent advances in the field and propose a theoretical model of motor control that may contribute to a better understanding of the pathophysiology of movement disorders such as Parkinson’s disease

Substrats cérébraux des processus moteurs automatiques et inconscients

Les mécanismes à la base des troubles du contrôle moteur sont encore peu compris. L'étude des patients akinétiques et hyperkinétiques soulignent l’importance physiopathologique du cortex (pré)moteur et des noyaux gris centraux. Ces études ne nous permettent cependant pas de déterminer le rôle respectif de ces différentes régions. Les modèles actuels suggèrent que certains mouvements anormaux résultent d’une perturbation de l’équilibre entre les processus de facilitation et d’inhibition des programmes moteurs secondaire à une altération de l’intégration perceptuo-motrice. Dans le cadre de ce travail, nous avons utilisé une tâche d'amorçage subliminale afin d'examiner les corrélats cérébraux de ces processus chez des sujets jeunes ainsi que chez des patients atteints de la maladie de Parkinson. Nous avons montré que l'activation/facilitation et l'inhibition automatiques et inconscientes étaient sous-tendues par un réseau moteur cortico-sous-cortical. Ce résultat a été ensuite confirmé au moyen d'une approche lésionnelle par l'étude de patients parkinsoniens. Nous avons également mis en évidence une dépendance cingulo-préfrontale dans la détection /résolution de conflit inconscient. Ces résultats remettent en cause les théories traditionnelles considérant la conscience et le contrôle cognitif comme étant étroitement reliés et contribue à une meilleure compréhension de la physiopathologie des mouvements anormaux

Etude des processus inconscients d'auto-activation et d'auto-inhibition de l'action motrice par imagerie par résonance magnétique fonctionnelle

Bien que plusieurs recherches aient soulignées l’importance des mécanismes automatiques et inconscients dans le contrôle de l’action motrice, les substrats neuronaux impliqués dans ce genre de processus sont encore peu connus. En effet, les expérimentations précédentes ont démontré une implication de certaines régions cérébrales en utilisant uniquement pour la plupart une approche lésionnelle. Ce travail avait donc pour but d’identifier les corrélats cérébraux de ces processus au moyen de l’imagerie par résonance magnétique fonctionnelle, pendant l’administration d’une tâche d’amorçage subliminal masquée à des volontaires sains. Dans cette tâche visuomotrice, les sujets doivent répondre le plus rapidement possible à une flèche cible congruente ou non avec l’amorce subliminale cachée qui la précède. Ce paradigme permet, en manipulant l’intervalle entre le masque et la cible, de mettre en évidence un effet de compatibilité positive ou négative sur les temps de réaction. L’effet de compatibilité négative (ECN) a été interprété comme une conséquence d’une inhibition automatique qui supprime l’activation motrice produite par l’amorce. L’ECN engendre un conflit de réponse, les sujets mettant donc un temps plus important pour répondre à une flèche qui a été préalablement inhibée. Nous avons, dans un premier temps, répliqué les résultats comportementaux de la tâche d’amorçage subliminal masquée. Dans un second temps, en accord avec les autres études dans le domaine, nous avons démontré que la simple perception inconsciente d’un stimulus pouvait activer les régions cérébrales sous-tendant la représentation, la sélection et l’initiation de l’action motrice, alors que l’inhibition se traduit principalement par une diminution de l’activité de ces régions. Cette découverte apporte une nouvelle contribution à l’explication de la pathophysiologie des troubles hyperkinétiques

Evidence for distinct roles for basal ganglia and SMA in automatic and unconscious inhibition of voluntary actions

Introduction: Although previous research highlighted the importance of automatic and unconscious inhibition in motor control, the neural correlates of such processes remain unclear. Basal ganglia dysfunctions have long been associated with impairment in automatic motor control. In addition, Sumner & al. (2007) suggested a key role of the medial frontal cortex by administrating a masked priming task (e.g., Eimer & Schlaghecken 2003) to a patient with a small lesion restricted to the supplementary motor area (SMA)., Here, we used fMRI in normal subjects to better delineate the respective roles of SMA and basal ganglia in automatic and unconscious motor inhibition. Methods: We used event-related BOLD fMRI at 3T to record brain activity in 26 healthy volunteers (22 ± 2 years) as they performed the subliminal masked priming task. In this visuomotor task, participants are asked to make speeded button presses with the left or right hand following leftward or rightward pointing arrows, which are preceded by masked prime arrows. Here, two experimental variables were manipulated: the interval between the mask and the target (SOA: 0,100,150,200 or 250 ms) and the prime/target direction (compatible or incompatible). Imaging data processing and analysis were performed using SPM8b. Results: using Repeated Measures ANOVA of behavioral data (global interaction SOA*compatibility, p0.05) By applying a similar statistical model to imaging data, we observed a stronger activity in the in several regions, the SMA (p<0.001, uncorrected), caudate (p=0.002, uncorrected) and thalamus (p<0.001, uncorrected) showing stronger activity in compatible than incompatible trials at 100 and 150-SOA, as compared with 0-SOA. Moreover, the differential activity in the SMA was correlated with the negative compatibility effect (p= 0.01). When testing for a main effect of SOAs we didn’t find a differential activation of the SMA, but a stronger deactivation of the caudate (p=0.009, uncorrected) and the thalamus (p=0.007, uncorrected) at 100-150 SOA (inhibition conditions) compared to 0-SOA (facilitation condition). In a prime identification task administered after the fMRI experiment, subjects’ performance was at chance levels for primes displayed for 17 ms as in the main study, suggesting that the prime was not consciously perceived. Conclusions: These new findings suggest that automatic and unconscious inhibition of an activated motor response is mediated by the basal ganglia whereas medial frontal regions seem to be more implicated in the control of response conflict related to inhibition

Invasive and Non-invasive Electrical Pericranial Nerve Stimulation for the Treatment of Chronic Primary Headaches

Chronic primary headaches are widespread disorders which cause significant quality of life and socioprofessional impairment. Available pharmacological treatments have often a limited efficacy and/or can generate unbearable side effects. Electrical nerve stimulation is a well known non-destructive method of pain modulation which has been recently applied to headache management. In this review, we summarise recent advances in invasive and non-invasive neurostimulation techniques targeting pericranial structures for the treatment of chronic primary headaches, chiefly migraine and cluster headache: occipital nerve, supraorbital nerve, vagus nerve, and sphenopalatineganglion stimulations. Invasive neurostimulation therapies have offered a new hope to drug-refractory headache sufferers but are not riskless and should be proposed only to chronic patients who failed to respond to most existing preventives. Non-invasive neurostimulation devices are user-friendly, safe and well tolerated and are thus taking an increasing place in the multidisciplinary therapeutical armamentarium of primary headaches

Métabolisme cérébral distinct en relation avec la sensibilité à la douleur entre sujets sains, migraine épisodique et migraine chronique

Introduction Allodynia, i.e. pain evoked by a non-painful stimulus, is prevalent in chronic pain and in migraine where it augments with disease severity and chronicity [1]. Central sensitization is thought to be the culprit [2]. It is not known, however, which central areas are involved. The aim of the present study was to evaluate whether brain metabolism in subjects that are more sensitive to pain is different between migraine patients and healthy controls. Subjects and methods Quantitative heat sensory testing on the forehead and 18FDG-PET were performed in 55 subjects: 20 healthy volunteers (HV, 21-59 years, 5M), 21 patients with episodic migraine in the interictal phase (MO, age range: 20-63 years, 5M) and 14 patients with chronic migraine (CM, age range: 22-62 years, 1M). The 3 cohorts were subdivided according to the median heat pain threshold into subgroups with low and high pain thresholds. PET results were compared between these subgroups in each cohort. Data analyses were restricted to areas of the pain/salience matrix. Results There was no significant difference in heat pain thresholds between HV (median: 43.7 °C), MO median: 44.2°C) and CM (median: 43.3°C) (p=0.64). In an SPM-ANOVA, a contrast modelling the potential gradual effect of increased differences in pain sensitivity in relation to disease severity showed significant metabolic changes in bilateral thalamus and midbrain (p < 0.001). Additional analyses revealed that hypometabolic areas in subgroups with a low heat pain threshold differed between HV (anterior cingulate and somatosensory cortices), MO (lower pons and somatosensory cortex) and CM (midbrain and thalamus) (Figure 1). Conclusion Overall migraine patients do not have reduced heat pain thresholds. However, hypometabolic areas related to high thermal pain sensitivity are strictly cortical in HV, but comprise the pons in episodic migraine and are restricted to midbrain and thalamus in chronic migraine. The distinct central correlates of heat pain sensitivity in migraine patients might therefore represent a biomarker of migraine and its chronification. Legend to figure Figure 1. Hypometabolic areas in low pain threshold subgroups in HV (green), MO (orange) and CM (red). p < 0.01 for display purpose.Les migraineux ont une sensibilité anormale à la douleur. Les mécanismes cérébraux en sont inconnus. Nous avons comparé le métabolisme cérébral chez des sujets sains et chez des migraineux épisodiques ou chroniques et correlé les résultats avec le seuil douloureux. Les aires cérébrales hypométaboliques liées à un seuil douloureux bas diffèrent entre groupes: régions corticales chez les sujets sains, aires corticales et sous-corticales dans la migraine épisodique, régions sous-corticales dans la migraine chronique .Le contrôle central de la douleur semble modifié distinctement dans les formes de migraine, ce qui pourrait en constituer un biomarqueur et avoir des implications thérapeutiques