Slow cortical potentials in migraine families

Amplitude and habituation of event-related potentials are abnormal in migraine. We investigated 43 migraine and 41 healthy families to evaluate the influences of age, sex and familial contribution on the variance of amplitude and habituation of the contingent negative variation (CNV). Analysis of individual differences in relation to the CNV habituation was performed. The study demonstrated that habituation of the early CNV component characterizes migraine considerably better than the CNV amplitudes. Habituation, however, is strongly influenced by age. Migraine adults and children generally showed reduced habituation. Surprisingly, more than 30% of the healthy adults demonstrated a marked loss of habituation. The reduced CNV habituation represented a high sensitivity but low specificity to migraine, especially in children. CNV amplitude and habituation parameters revealed a considerable familial contribution associated with migraine. No familial influence on either morphology or habituation of the CNV in healthy families or between healthy members of migraine families was observed. The low specificity and familial transmission of CNV parameters in members of migraine families suggest that increased amplitudes and reduced habituation of CNV do not constitute a primary risk factor for migraine, but rather represent a predisposition. Genetic components probably affect variation of the CNV amplitude and habituation.     

Subtle grey matter changes between migraine patients and healthy controls

Local morphological alterations of the brain have recently been detected in cluster headache and chronic tension-type headache, but not in migraine. We investigated 35 patients suffering from migraine and compared them with 31 healthy controls with no headache history. Using magnetic resonance imaging and voxel based morphometry, we found a significant decrease of grey matter in areas ascribable to the transmission of pain (cingulate cortex), but not in areas specific for migraine, such as the brainstem. Our data are in line with recent findings in chronic pain states, such as chronic phantom pain and chronic back pain. We suggest that the grey matter change in migraine patients is the consequence of frequent nociceptive input and should thus be reversible when migraine attacks cease.     

Effects of topiramate on migraine frequency and cortical excitability in patients with frequent migraine

We studied the excitability of the visual and motor cortex in 36 patients with frequent migraine without aura (30 women, mean age 38.6 ± 10.0 years) before and after treatment with topiramate (100 mg/day) using transcranial magnetic stimulation. Treatment with topiramate resulted in reduction of both headache frequency (12.0 ± 1.3 to 5.8 ± 3.2 migraine days per month; P  = 0.004) and cortical excitability: motor cortex thresholds increased on the right side from 43.8 ± 7.5% to 47.7 ± 9.2% ( P  = 0.049) and on the left side from 43.4 ± 7.0% to 47.2 ± 9.6% ( P  = 0.047), and phosphene thresholds increased from 58.9 ± 11.1% to 71.2 ± 11.2% ( P  = 0.0001). Reduction of headache frequency correlated inversely with an increase of visual thresholds and did not correlate with motor thresholds. The effect of topiramate in migraine prevention is complex and can not be explained simply by inhibition of cortical excitability.     

Event-related slow potentials and associated catecholamine function in migraine

Plasma norepinephrine and dopamine and event-related slow potentials were measured at menses and ovulation in migraine with and without aura relative to normal subjects. The results indicated that at menses, but not ovulation, plasma dopamine was increased and norepinephrine was decreased relative to normal. This catecholamine imbalance was greater in migraine without aura than in migraine with aura. Conversely, event-related slow potentials measured over the posterior cortex at ovulation but not at the menses was altered relative to normal. Early epoch negativity was reduced in migraine with aura, whereas late epoch negativity was reduced in migraine without aura. The results suggested that (a) migraine without aura may involve dynamic shifts in the function of both norepinephrine and dopamine responsive neurons; (b) pathophysiology of migraine with aura is less dependent on catecholamine imbalance (norepinephrine alone affected); (c) these pathophysiological mechanisms are most prevalent in or restricted to posterior cortical regions but may be modulated by brainstem mechanisms.     

Effects of remote cutaneous pain on trigeminal laser-evoked potentials in migraine patients

The present study aimed to evaluate heat pain thresholds and evoked potentials following CO₂ laser thermal stimulation (laser-evoked potentials, LEPs), during remote application of capsaicin, in migraine patients vs. non-migraine healthy controls. Twelve outpatients suffering from migraine without aura were compared with 10 healthy controls. The LEPs were recorded by 6 scalp electrodes, stimulating the dorsum of the right hand and the right supraorbital zone in basal condition, during the application of 3% capsaicin on the dorsum of the left hand and after capsaicin removal. In normal subjects, the laser pain and the N2-P2 vertex complex obtained by the hand and face stimulation were significantly reduced during remote capsaicin application, with respect to pre-and post-capsaicin conditions, while in migraine LEPs and laser pain were not significantly modified during remote painful stimulation. In migraine a defective brainstem inhibiting control may coexist with cognitive factors of focalised attention to facial pain, less sensitive to distraction by a second pain.     

Contingent negative variation during migraine attack and interval: evidence for normalization of slow cortical potentials during the attack

The contingent negative variation (CNV) amplitudes of 16 subjects with migraine without aura were studied during pain-free intervals and during attacks and the results were compared with those of 22 healthy subjects. In 32 trials the CNV amplitudes were calculated for (a) "total interval", (b) "early CNV component", (c) "late CNV component", and (d) habituation. There was a significantly higher total CNV amplitude in migraine subjects during pain-free intervals compared to that of the healthy subjects and migraine patients during an attack. Healthy subjects as well as subjects studied during the attack showed a significant habituation whereas migraine subjects studied during pain-free intervals did not. This suggests that the higher CNV amplitude in migraine patients studied between pain-free attacks may be due in part to impaired habituation.     

Intensity dependence of auditory evoked cortical potentials in migraine families

Intensity dependence of auditory evoked cortical potentials is abnormal in migraine. This study investigated intensity dependence in migraine and healthy families using group comparisons and analysis of individual differences. Migraineurs were characterized by a steeper amplitude/stimulus function slope and more pronounced difference between the amplitudes of N1-P2 on the more and the less intensive tones than healthy age matched subjects. Apart from migraine, the age of the participants was an important predictive variable of intensity dependence. Analysis of individual differences revealed low sensitivity and moderate specificity of intensity dependence for migraine. Familial prevalence of intensity dependence among first-degree relatives in migraine families was equal to that in healthy families. These findings support the assumption that high-intensity dependence reflects a functional CNS trait which is more pronounced and prevalent in migraine, but may also be found in healthy individuals and in other neuropsychiatric disorders. Increased intensity dependence is only one of several factors contributing to the risk for this form of headache.     

Cerebrospinal fluid analyses in migraine patients and controls

To investigate the role of central neurotransmitters in the pathogenesis of migraine, we measured cerebrospinal fluid (CSF) levels of certain amino acids (glycine, taurine, glutamine) and metabolites of biogenic amines (5-hydroxyindoleacetic acid and homovanillic acid) in 38 migraine patients and compared them with the levels from 10 headache-free controls. The levels of taurine, glycine and glutamine were significantly higher in the migraine patients (p < 0.0001 for taurine and glycine; p < 0.0009 for glutamine); there were no significant differences among the three migraine subgroups (infrequent migraine, frequent migraine and transformed migraine). In seven patients subsequently treated with divalproex sodium, CSF taurine levels decreased significantly from pretreatment baseline values. These data support the concept that migraine is at least in part a disorder of central neurotransmission.     

Influence of colors on habituation of visual evoked potentials in patients with migraine with aura and in healthy volunteers

OBJECTIVE: To investigate whether colored glasses influence the habituation of visual evoked potentials. BACKGROUND: We have previously shown that during pattern-reversal stimulations lasting 2 minutes the amplitude of the visual evoked potential increases in migraine with and without aura between attacks, whereas it decreases in healthy volunteers. Red light was found to increase visually evoked EEG fast activity only in children with migraine with aura. Wearing rose-tinted glasses for 4 months decreased attack frequency in parallel with a reduction of the visually evoked EEG fast activity. METHODS: We compared the change in amplitude of the visual evoked potential using five different tinted glasses in 12 patients with migraine with aura and in 10 healthy volunteers. During continuous stimulation at 3.1 Hz, five blocks of 50 responses were sequentially averaged using red, yellow, green, blue, and grey glasses and without glasses in a random order and analyzed in terms of latencies and N1-P1 amplitudes. Amplitude changes were calculated for each block by comparison with the first block in every condition and analyzed statistically using Zerbe's method. RESULTS: In healthy volunteers, the visual evoked potential amplitude increased with red glasses compared to without glasses (P = .05) or with green glasses (P = .03). In patients with migraine with aura, no significant difference was detected using colored glasses. Our findings in healthy volunteers are in line with earlier reports of increased excitability of the human visual cortex when exposed to red light. The lack of such a pattern in patients with migraine with aura suggests that the visual cortex is interictally hypoexcitable rather than hyperexcitable, which is consistent with studies of transcranial magnetic stimulation.     

偏头痛患者事件相关诱发电位的特点

目的:通过测定偏头痛患者早期认知功能障碍的指标P300听觉事件相关诱发电位,分析偏头痛患者的认知功能特点。方法:选择2005-01/12在北京大学人民医院神经内科门诊就诊的偏头痛患者56例,同时选取在本院门诊就诊及进行体检的52名健康人作为正常对照组,均自愿参加观察。采用肌电诱发电位仪检测以上两组观察对象的听觉事件相关诱发电位P300,记录波型中P300的潜伏期和波幅。偏头痛组患者均行头颅MRI检查,观察有无异常。记录患者平均头痛发作频率、持续时间、头痛强度和头痛发作史,分析以上指标与听觉事件相关诱发电位P300潜伏期和波幅的相关性。结果:偏头痛组56例患者及正常对照组52名健康人全部进入结果分析,无脱落。①两组观察对象听觉事件相关电位P300的潜伏期和波幅比较:偏头痛组患者P300的潜伏期显著长于正常对照组眼(328.66±33.06,315.73±25.19)ms(t=-2.296,P<0.05)演,波幅显著低于正常对照组眼(11.17±2.05,11.99±1.71)μV(t=2.275,P<0.05)演。②偏头痛组头部MRI检查正常与异常患者听觉事件相关电位P300的潜伏期和波幅比较:56例偏头痛患者中25例异常,表现为皮质下脑白质病变,设为MRI检查异常组;其余31例设为MRI检查正常组。MRI检查异常组患者P300的潜伏期显著长于MRI检查正常组眼(349.88±17.07,311.55±33.06)ms(t=-5.597,P<0.01)演,波幅显著低于MRI检查正常组眼(9.61±1.08,12.42±2.05)μV(t=7.355,P<0.01)演。③偏头痛患者病程与听觉事件相关电位P300的潜伏期呈正相关(P<0.01),与波幅呈负相关(P<0.01)。结论:偏头痛患者存在脑认知功能障碍,且认知障碍程度与病程长短有关,病程越长,程度越重。偏头痛患者可出现脑白质区病变,此病变加重了认知功能障碍。     

偏头痛患者事件相关诱发电位的特点

目的：通过测定偏头痛患者早期认知功能障碍的指标P300听觉事件相关诱发电位，分析偏头痛患者的认知功能特点。 方法：选择2005-01／12在北京大学人民医院神经内科门诊就诊的偏头痛患者56例，同时选取在本院门诊就诊及进行体检的52名健康人作为正常对照组，均自愿参加观察。采用肌电诱发电位仪检测以上两组观察对象的听觉事件相关诱发电位P300，记录波型中P300的潜伏期和波幅。偏头痛组患者均行头颅MRI检查，观察有无异常。记录患者平均头痛发作频率、持续时间、头痛强度和头痛发作史，分析以上指标与听觉事件相关诱发电位P300潜伏期和波幅的相关性。 结果：偏头痛组56例患者及正常对照组52名健康人全部进入结果分析，无脱落。①两组观察对象听觉事件相关电位P300的潜伏期和波幅比较：偏头痛组患者P300的潜伏期显著长于正常对照组[（328．66&;#177;33．06，315．73&;#177;25．19）ms（t=-2．296，P〈0．05）]，波幅显著低于正常对照组[（11．17&;#177;2．05，11．99&;#177;1．71）μV（t=2．275，P〈0．05）]。②偏头痛组头部MRI检查正常与异常患者听觉事件相关电位P300的潜伏期和波幅比较：56例偏头痛患者中25例异常，表现为皮质下脑白质病变，设为MRI检查异常组；其余31例设为MRI检查正常组。MRI检查异常组患者P300的潜伏期显著长于MRI检查正常组[（349．88&;#177;17．07，311．55&;#177;33．06）ms（t=-5．597，P〈0．01）]，波幅显著低于MRI检查正常组[（9．61&;#177;1．08，12．42&;#177;2．05）μV（t=7．355，P〈0．01）]。③偏头痛患者病程与听觉事件相关电位P300的潜伏期呈正相关（P〈0．01），与波幅呈负相关（P〈0．01）。 结论：偏头痛患者存在脑认知功能障碍，且认知障碍程度与病程长短有关，病程越长，程度越重。偏头痛患者可出现脑白质区病变，此病变加重了认知功能障碍。     

Effects of distraction versus spatial discrimination on laser-evoked potentials in migraine

OBJECTIVES: To evaluate whether migraine patients exhibit less inhibition to painful stimuli when distracted from pain as compared to healthy subjects, testing the spatial discrimination of painful stimuli, the performance during the mental arithmetic task used to contrast the discrimination performance and the behavior of N1 and N2-P2 laser-evoked potentials (LEPs) amplitudes during spatial discrimination and during distraction. METHODS: Eight migraine patients and 8 healthy controls were examined. During repetitive series of painful laser stimulation of the hand, they had to (1) perform a spatial discrimination task, contrasted by (2) a mental arithmetic task that served as distraction. RESULTS: Patients made 50% to 100% more mistakes than controls in the spatial discrimination task (P < .001) as well as during mental arithmetic (P < .05). Whereas healthy subjects showed a marked decrease of the LEP vertex potential amplitudes during distraction compared to the discrimination task, no such attenuation of LEPs was seen in migraine patients (group x task interaction, P < .05). N1 amplitude exhibited a left-hemisphere dominance in both groups, significantly smaller amplitude in migraine patients, but no significant task modulation. CONCLUSION: Migraine patients exhibited reduced inhibition by attentional modulation of pain processing, accompanied by impaired spatial discrimination of painful stimuli.     

Brain-computer communication: self-regulation of slow cortical potentials for verbal communication.

OBJECTIVE: To test a training procedure designed to enable severely paralyzed patients to communicate by means of self-regulation of slow cortical potentials. DESIGN: Application of the Thought Translation Device to evaluate the procedure in patients with late-stage amyotrophic lateral sclerosis (ALS). SETTING: Training sessions in the patients' homes. PARTICIPANTS: Two male patients with late-stage ALS. INTERVENTIONS: Patients learned voluntary control of their slow cortical potentials by means of an interface between the brain and a computer. Training was based on visual feedback of slow cortical potentials shifts and operant learning principles. The learning process was divided into small steps of increasing difficulty. MAIN OUTCOME MEASURES: Accuracy of self-control of slow cortical potentials (percentage of correct responses). Learning progress calculated as a function of training session. RESULTS: Within 3 to 8 weeks, both patients learned to self-regulate their slow cortical potentials and to use this skill to select letters or words in the Language Support Program. CONCLUSIONS: This training schedule is the first to enable severely paralyzed patients to communicate without any voluntary muscle control by using self-regulation of an electroencephalogram potential only. The protocol could be a model for training patients in other brain-computer interface techniques.     

Effective connectivity among brain regions associated with slow temporal summation of C-fiber-evoked pain in fibromyalgia patients and healthy controls

Temporal summation of "second pain" (TSSP) or "windup" results from the summation of C-fiber-evoked responses of dorsal-horn neurons. This phenomenon is dependent on stimulus frequency (≥.33 Hz) and relevant to central sensitization and chronic pain. Our previous neuroimaging studies characterized brain regions associated with TSSP in normal control (NC) and fibromyalgia (FM) groups. During an fMRI scan, subjects received sensitivity-adjusted repetitive heat pulses at .33 on the right foot. FM subjects required significantly lower stimulus intensities than NC to achieve similar TSSP and no significant group differences in the pain-related brain activity were detected. In our current study, we asked whether the effective connectivity among a set of TSSP-related brain regions identified in our previous work differs amongst FM and NC groups. Structural equation modeling was used to characterize the effective connectivity amongst a priori selected brain areas, including the thalamus, S1, S2, posterior insula, and the anterior midcingulate cortex (aMCC) within the left and right hemispheres. This analysis confirmed our a priori models of effective connectivity among these regions mainly confirmed those hypothesized, yet some unpredicted connections were additionally identified (thalamus to aMCC and aMCC to S1). While the models of effective connectivity were not identical in the FM and NC groups, they were very similar. Additionally, the TSSP related effective connectivity of right and left hemisphere regions was very similar. These results provide evidence for significant overlap of the fundamental brain mechanisms that process sensory and affective information related to TSSP in NC and FM groups. PERSPECTIVE: Models of effective connectivity involving pain-related processes were estimated with fMRI data from chronic pain and healthy populations. Models were estimated in both hemispheres, and although similar, fibromyalgia was associated with unique models of pain-related processes. Group differences involved the left hemisphere and S1, S2, and posterior insula.     

Brain activity associated with slow temporal summation of C‐fiber evoked pain in fibromyalgia patients and healthy controls

Temporal summation of “second pain” (TSSP) is the result of C‐fiber‐evoked responses of dorsal‐horn neurons, termed “windup”. This phenomenon is dependent on stimulus frequency (≥0.33Hz) and relevant for central sensitization as well as chronic pain. Whereas, our previous functional magnetic resonance imaging (fMRI) study characterized neural correlates of TSSP in 11 healthy volunteers, the present study was designed to compare brain responses associated with TSSP across these healthy participants and 13 fibromyalgia (FM) patients. Volume‐of‐interest analysis was used to assess TSSP‐related brain activation. All participants underwent fMRI‐scanning during repetitive heat pulses at 0.33Hz and 0.17Hz to the right foot. Stimulus intensities were adjusted to each individual's heat sensitivity to achieve comparable TSSP‐ratings of moderate pain in all subjects. Experimental pain ratings showed robust TSSP during 0.33Hz but not 0.17Hz stimuli. When stimulus strength was adjusted to induce equivalent levels of TSSP, no differences in activation of pain‐related brain regions occurred across NC and FM groups. Subsequently, the fMRI‐data of both groups were combined to increase the power of our statistical comparisons. fMRI‐statistical maps identified several brain regions with stimulus and frequency dependent activation consistent with TSSP, including ipsilateral and contralateral thalamus, medial thalamus, S1, bilateral S2, mid‐ and posterior insula, rostral and mid‐anterior cingulate cortex. However, the stimulus temperatures necessary to evoke equivalent levels of TSSP and corresponding brain activity were less in FM patients. These results suggest that enhanced neural mechanisms of TSSP in FM are reflected at all pain related brain areas, including posterior thalamus, and are not the result of selective enhancement at cortical levels.     

Effects of fluoxetine on habituation of pattern reversal visually evoked potentials in migraine prophylaxis

OBJECTIVE: To investigate the effects of fluoxetine in migraine prophylaxis on habituation of visually evoked potentials. BACKGROUND: Habituation of pattern reversal visually evoked potentials was found to be abnormal in migraine between attack, and this abnormality was most likely due to serotonergic pathway dysfunction in the brain stem. METHODS: One hundred nineteen subjects were included in the study: 40 healthy volunteers and 79 migraineurs not taking any prophylactic migraine medication (44 without aura and 35 with aura). Visually evoked potentials in migraineurs were recorded in the headache-free interval. Amplitude change of the visually evoked potentials (N1-P1) was measured between the first and fifth block of 50 sequential averagings during continuous stimulation at 3.1 Hz. All migraineurs were placed on fluoxetine 20 mg/day for prophylaxis of migraine. One month later, visually evoked potentials were recorded again. RESULTS: Mean amplitude changes in the fifth block expressed as percentages of the first block were -13.4% +/- 19.2% in healthy volunteers, 9.8% +/- 23.3% in migraine without aura, and 4.4% +/- 8.7% in migraine with aura during the baseline period. The difference was significant between migraineurs and healthy volunteers (both P= 0.0001), but not between migraineur groups. After treatment, amplitude changes were -9.3% +/- 14.5% in migraine without aura and -10.1% +/- 11.5% in migraine with aura. Habituation pattern tended to normalize with prophylactic treatment, and mean amplitude changes were not significant between migraineurs and healthy volunteers (both P = 0.4). CONCLUSIONS: We concluded that the fluoxetine prophylaxis corrects the interictal deficit of habituation in migraineurs.     

Shortened cortical silent period in facial muscles of patients with migraine

Despite intensive neurophysiological research, evidence is lacking to show whether abnormal cortical excitability in migraine reflects a primary cortical disturbance or reduced control by thalamo-cortical loops. One way to contribute to the scientific discussion on this topic is to deliver transcranial magnetic stimulation (TMS) and test the cortical silent period (SP) recorded in facial muscles. The facial-muscle SP is a purely cortical phenomenon that reflects the excitability of inhibitory interneurons, and can disclose changes in cortical inhibition even in patients without documented primary lesions of the motor cortices. To test the interictal excitability of cortical motor inhibitory interneurons in migraine, we investigated the facial-SP in patients with migraine with and without aura between attacks. In 26 patients and 15 age-matched controls, high-intensity magnetic stimuli were delivered with a round coil centered at the vertex during a maximal muscle contraction. Electromyographic responses were recorded from surface electrodes placed over the subjects' perioral muscles. Facial SPs were significantly shorter in patients than in controls. The SP shortening provides neurophysiological evidence showing hypoexcitability of cortical inhibitory neurons in patients with migraine between attacks. Despite a possible primary deficit of cortical inhibitory interneurons in migraine, we favor the interpretation of a secondary disfacilitation by hypoactive thalamo-cortical loops. Based on this interpretation, the interictal reduced cortical inhibition documented by the shortened SP could be considered the motor counterpart of the reduced preactivation excitability level in the sensory cortices purported to explain why cortical evoked responses habituate poorly in patients with migraine.     

Effects of symptomatic treatments on cutaneous hyperalgesia and laser evoked potentials during migraine attack

Previously an amplitude enhancement of laser evoked potentials (LEPs) was detected during migraine attack: we further examined pain threshold to CO2 laser stimuli and LEPs during attacks, evaluating the effect of almotriptan, lysine-acetylsalicylate and placebo treatment on cutaneous hyperalgesia to thermal stimuli delivered by CO2 laser and on LEP components. Eighteen patients suffering from migraine without aura were analysed. They were divided into three groups of six patients each, randomly assigned to lysine acetyl-salicylate, almotriptan or placebo treatments. The supraorbital zones and the dorsum of the hand were stimulated on both the symptomatic and not symptomatic side in all patients. The LEPs were recorded by 25 scalp electrodes. During attacks, the P2 wave was significantly enhanced; the amplitude of the P2 component obtained by the stimulation of the supraorbital zone during the attack on the side of the headache was significantly correlated with the intensity of pain and the frequency of headache. Both almotriptan and lysine acetyl-salicylate significantly reduced the P2 amplitude but they showed no effects on hyperalgesia to laser stimulation; headache relief following therapy was correlated with the reduction of the P2 amplitude. The cortical elaboration of laser-induced experimental pain seemed increased during migraine attack, and the severity of headache was mainly related to the increase of the later LEPs components expressing the attentive and emotive compounds of suffering. Reversion of this process appeared to be primarily responsible for the efficacy of drugs in treating migraine, though both almotriptan and lysine-acetil salicilate seemed to have no effect in reducing sensitization at second and third order nociceptive neurons.