Cortical inhibition and habituation to evoked potentials: relevance for pathophysiology of migraine. J Headache Pain

Dipartimento di Neuroscienze Cliniche, University of Palermo, Via G. la Loggia, 1, 90129 Palermo, Italy.
The Journal of Headache and Pain (Impact Factor: 2.8). 03/2009; 10(2):77-84. DOI: 10.1007/s10194-008-0095-x
Source: PubMed


Dysfunction of neuronal cortical excitability has been supposed to play an important role in etiopathogenesis of migraine. Neurophysiological techniques like evoked potentials (EP) and in the last years non-invasive brain stimulation techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation gave important contribution to understanding of such issue highlighting possible mechanisms of cortical dysfunctions in migraine. EP studies showed impaired habituation to repeated sensorial stimulation and this abnormality was confirmed across all sensorial modalities, making defective habituation a neurophysiological hallmark of the disease. TMS was employed to test more directly cortical excitability in visual cortex and then also in motor cortex. Contradictory results have been reported pointing towards hyperexcitability or on the contrary to reduced preactivation of sensory cortex in migraine. Other experimental evidence speaks in favour of impairment of inhibitory circuits and analogies have been proposed between migraine and conditions of sensory deafferentation in which down-regulation of GABA circuits is considered the more relevant pathophysiological mechanism. Whatever the mechanism involved, it has been found that repeated sessions of high-frequency rTMS trains that have been shown to up-regulate inhibitory circuits could persistently normalize habituation in migraine. This could give interesting insight into pathophysiology establishing a link between cortical inhibition and habituation and opening also new treatment strategies in migraine.

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Available from: Filippo Brighina, Oct 08, 2015
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    • "Habituation indeed is a general physiological phenomenon and is not specific for visual input. On the other hand impairment of habituation, would not be specific of migraine because a defective ability to habituate to sensory stimulation has been described also in other pathological brain conditions and hypothesized to depend upon dysfunction of cortical activation, principally to defective cortical inhibition (Brighina et al., 2009). An example of such combined dysfunctions could be Parkinson's disease (PD) where habituation and inhibitory cortical circuits are impaired and can both be restored by effective L-DOPA treatment that has been shown to reset cortical inhibition in this disease. "
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 06/2015; DOI:10.1016/j.clinph.2015.05.028 · 3.10 Impact Factor
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    • "Recently, non-invasive brain stimulation has been used to induce durable changes in cortical excitability and potentially correct the neural activity abnormalities found in migraine patients. However, as it is not clear whether the symptoms of migraine result on a hyper-[4] [5] or a hypoexcitability of the visual cortex [6] [7] [8] different stimulation paradigms have been applied depending on the author's hypothesis whether the migraine brain is hyper-or hypoexcitable. For instance, in order to decrease or prevent symptoms of the disease, some authors applied inhibitory stimulations over the visual cortex to correct an eventual cortical hyperexcitability [9] [10]. "
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    ABSTRACT: The aims of this paper are (i) to compare the excitability of visual cortex in migraine patients with healthy volunteers; and (ii) if an abnormal excitability has been found, to modulate cortical excitability in migraine patients with transcranial direct current stimulation (tDCS) and observe their clinical and neurophysiological effects. The study was divided into two steps. A cross-sectional study (step 1) was conducted to compare the cortical excitability of 23 migraineurs (11 with and 12 without aura) on 11 healthy individuals. On step 2, a randomized, double blinded, controlled pilot trial was carried on with 19 migraineurs, randomly divided into: experimental and control group. During 12 sessions, experimental and group received active tDCS to visual cortex and control group received sham tDCS. The headache diary was applied for a total of 90days (before, during and after tDCS sessions). Phosphene threshold (PT) induced by transcranial magnetic stimulation was recorded to measure the excitability of the visual cortex before and after each session. Step 1 showed higher level of cortical excitability between migraineurs when compared to healthy volunteers; therefore, cathodal tDCS was applied over visual cortex in step 2. After tDCS application, a significant decrease was observed in a number of migraine attacks, painkiller intake and duration of each attack just in experimental group. The analysis of PT indicated no difference in cortical excitability after tDCS. Findings of the study suggested that inhibitory tDCS on visual cortex might be an alternative and non-pharmacological treatment for migraine prophylaxis. However the clinical improvements of patients after tDCS treatment are not correlated with changes in cortical excitability. Copyright © 2014. Published by Elsevier B.V.
    Journal of the Neurological Sciences 12/2014; 349(1-2). DOI:10.1016/j.jns.2014.12.018 · 2.47 Impact Factor
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    • "As mentioned above, the neural mechanisms underlying habituation remain poorly understood, and this uncertainty helps to explain why the abnormal habituation pattern in migraine still lacks a definitive consensual interpretation [93-95]. "
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    ABSTRACT: The phenomena of habituation and sensitization are considered most useful for studying the neuronal substrates of information processing in the CNS. Both were studied in primary headaches, that are functional disorders of the brain characterized by an abnormal responsivity to any kind of incoming innocuous or painful stimuli and it's cycling pattern over time (interictal, pre-ictal, ictal). The present review summarizes available data on stimulus responsivity in primary headaches obtained with clinical neurophysiology. In migraine, the majority of electrophysiological studies between attacks have shown that, for a number of different sensory modalities, the brain is characterised by a lack of habituation of evoked responses to repeated stimuli. This abnormal processing of the incoming information reaches its maximum a few days before the beginning of an attack, and normalizes during the attack, at a time when sensitization may also manifest itself. An abnormal rhythmic activity between thalamus and cortex, namely thalamocortical dysrhythmia, may be the pathophysiological mechanism subtending abnormal information processing in migraine. In tension-type headache (TTH), only few signs of deficient habituation were observed only in subgroups of patients. By contrast, using grand-average responses indirect evidence for sensitization has been found in chronic TTH with increased nociceptive specific reflexes and evoked potentials. Generalized increased sensitivity to pain (lower thresholds and increased pain rating) and a dysfunction in supraspinal descending pain control systems may contribute to the development and/or maintenance of central sensitization in chronic TTH. Cluster headache patients are chrarcterized during the bout and on the headache side by a pronounced lack of habituation of the brainstem blink reflex and a general sensitization of pain processing. A better insight into the nature of these ictal/interictal electrophysiological dysfunctions in primary headaches paves the way for novel therapeutic targets and may allow a better understanding of the mode of action of available therapies.
    The Journal of Headache and Pain 07/2013; 14(1):65. DOI:10.1186/1129-2377-14-65 · 2.80 Impact Factor
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