Contingent negative variation before and after hemodialysis among patients with end-stage renal disease

OBJECTIVE: To investigate changes in contingent negative variation (CNV) induced by uremia and to study the effects of hemodialysis. METHODS: Fifteen right-handed healthy subjects and 12 patients with end-stage renal disease (ESRD) were studied. CNV was recorded from the Fz, Cz and Pz (using the International 10-20 System) referenced to linked ear lobes, using an S1 (click)-S2 (flashes)-key press paradigm. The amplitude of initial CNV (iCNV) was calculated as the average amplitude at 550-750 ms after S1. The amplitude of late CNV (lCNV) was the mean amplitude of the last 200 ms before S2. Testing was repeated for the patient group at pre- and post-hemodialysis observations. Neuropsychological measurements, a trail making test (TMT) and mini-mental state examination (MMSE), were conducted at each time. RESULTS: The mean amplitudes of iCNV and lCNV at the vertex (Cz) were both significantly lower in the patient group than in the control group (P<0.05). TMT were also significantly different between patient and control groups (P<0.05)), however MMSE showed no significant difference. There were no significant correlations between the values of neuropsychological tests and the parameters of CNV. Both iCNV and lCNV were not significantly different between the pre- and post-dialysis tests. CONCLUSION: CNV negativity in patients with ESRD reflects diffuse nonlocalizing neurological symptoms of uremia rather than a selective involvement of the frontal lobes. It is likely to reflect dysfunction in the frontal-subcortical circuit. In addition, hemodialysis seemed to have no significant effect on executive brain function in these patients with ESRD.     

How the brain anticipates an attack: a study of neurophysiological periodicity in migraine.

We investigated cortical excitability and the pattern of arousal in migraine patients using contingent negative variation (CNV) and EEG power spectrum analysis performed before and after a migraine attack. Twenty females suffering from migraine without aura and 12 healthy controls were enrolled in the study. In the group of patients, the CNV, EEG power spectrum and hemispheric asymmetry analyses were performed 1-4 days before the first day of an attack and 4 days following the last day with migraine. The recordings in healthy subjects were carried out on a day chosen by the participants. The comparisons were made using non-parametric procedures. After an attack no difference was found between patients and controls in EEG power spectrum, hemispheric asymmetry or CNV components (with the exception of the beta 1 power, which was more pronounced in patients). Before an attack, however, a significant increase in the power of delta and theta frequency bands, in the alpha asymmetry, and in early CNV amplitude were observed. The patients differed from controls both in the extent of cortical excitability and in the arousal pattern found. In such a way migraine is characterized by periodic CNV and EEG power spectrum changes during the pain-free interval. The abnormalities in cortical excitability and arousal were only observed before an attack, and could be used to predict the next migraine episode. We assume that these changes reflect the increased susceptibility of the migrainous brain to precipitating factors and the neurophysiological readiness to generate an attack. The time duration since the last attack must be taken into account when performing studies in the field of migraine research.     

Specific task anticipation versus unspecific orienting reaction during early contingent negative variation.

OBJECTIVE: To investigate whether a warning stimulus in a forewarned reaction time task elicits only an unspecific orienting reaction or task specific motor cortex activity. METHODS: We examined the time-course of alpha event-related desynchronization (ERD) as an indicator for primary motor cortex activation in an auditory contingent negative variation (CNV) paradigm with an interstimulus interval of 3 s in healthy subjects between 6 and 18 years using a 64 channel high-density sensor array. RESULTS: We replicated a wide frontal distribution for the initial CNV component (iCNV), while only during late CNV (lCNV) a centro-parietal negativity resembling the 'Bereitschaftspotential' occurred. However, an early alpha-ERD over the central area contralateral to the side of the response movement followed the imperative stimulus already during the iCNV-interval. This early alpha-ERD was highly significantly lateralised and was even more prominent during iCNV than during lCNV indicating an activation of the contralateral sensorimotor cortex already during iCNV. CONCLUSIONS: We conclude that early task specific preparatory motor processes (which might reflect the retrieval of a motor program from memory) were elicited by the warning stimulus. These preparatory processes clearly exceeded an unspecific orienting reaction as early alpha-ERD was influenced by the side of the anticipated movement.     

Time-dependent post-imperative negative variation indicates adaptation and problem solving in migraine patients

According to the Seligman theory of learned helplessness, depression is caused by a repetitive experience of loss of control resulting in internal, stable and global attributional styles for negative events. In depressed patients and healthy controls experiencing such events, an increased amplitude of the post-imperative negative variation (PINV) has been described. The aim of the study was to investigate a possible correlation between migraine, depression, learned helplessness and PINV. 24 patients suffering from migraine without aura and 24 healthy controls were exposed to a situation of loss of control whilst the contingent negative variation (CNV) from C3, C4 and Cz were recorded. Before conducting the experiment, the subjects were asked to answer the Beck Depression Inventory (BDI) and the German attributional style questionnaire (GASQ). Amplitudes of total CNV, early and late component and PINV were calculated in eight blocks of four recordings each. The results confirm findings of a pronounced PINV in situations of loss of control, though high amplitudes were not correlated with low values in the GASQ and therefore with learned helplessness. High PINV in migraine patients correlated with high scores in the BDI and the list of the complaints questionnaire. However, this was not the case in healthy controls. In this experimental situation, PINV in migraine patients can be interpreted as an expectancy potential in order to avoid failure and helplessness.     

Comparative study of the amplitude, surface and duration of the pre- and post-imperative waves of the CNV (contingent negative variation) in a group of 40 schizophrenic and schizo-affective patients as compared with normal subjects

In 27 normal adult subjects, pre- and postimperative phases of the CNV had an homogeneous pattern. The return to the baseline was of short duration (320 +/- 170 msec) whatever the amplitude and surface. This is in favor of an active mechanism terminating the CNV. In 27 schizophrenic and 13 schizoaffective patients, pre- and postimperative phases of the CNV were heterogeneous in character suggesting the possibility of multiple disturbances. When present, the preimperative negativity was of lower amplitude and had a delayed return to the baseline with a wider dispersion. In the patients with preimperative negativity followed by a PINV (postimperative negative variation), a linear relationship has been found between the amplitudes of the two waves.     

Contingent negative variation in headache

Contingent negative variation (CNV), an event-related slow cerebral potential, was analyzed in 79 consecutive headache patients. Compared to normal controls (n = 33), CNV did not differ in tension headache (n = 21) or in combined headaches with a predominant tension component (n = 13). The mean amplitude of CNV was significantly (p less than 0.001) increased in migraine (n = 29) as well as in combined headache with predominant migraine (n = 16). All migraineurs were studied between attacks and without prophylactic treatment. CNV may be a useful diagnostic test in headache. Its increased amplitude in migraine might reflect central catecholaminergic hyperactivity.     

军人创伤后应激障碍患者认知性电位变化及其与精神症状的关系

目的　探讨军人创伤后应激障碍(PSTD)患者认知性电位(CEP)的特征和治疗缓解后变化及其与精神症状的关系。方法　应用美国Nicolet Bravo型脑诱发电位仪,对 66 例发病期及其 60 例康复期 PTSD患者进行关联性负变(CNV)、视觉诱发电位(VEP)和听觉诱发电位(AEP)测定,并进行症状自评量表(SCL -90)和事件影响量表(IES)评定。结果　患者组发病期与对照组比较,CNV/M1、VEP/P2 和 AEP/N2 潜伏期延迟(P<0.01或0.05),CNV/M2 和AEP/P3 波幅增高(P<0.01),命令信号后负变化(PINV)出现率增高(P<0.01),SCL-90和IES总分及其部分因子分升高(P<0.01),且 CEP指标与 SCL 90 及 IES总分及其部分因子分显著相关(P<0.01 或 0.05)。患者组康复期 CNV/M1、VEP/P2 和 AEP/N2 潜伏期,CNV/M2、AEP/P3 波幅,PINV出现率以及SCL- 90和IES总分及其部分因子分均恢复至正常值内(与发病期比较P<0.01或0.05,与对照组比较 P>0.05)且治疗前后 CEP指标差值与 SCL 90 及 IES总分及其部分因子减分率显著相关(P<0.01或0.05)。结论　CNV、VEP与AEP的变化可能是PTSD的状态标志。     

Contingent Negative Variation Is Associated with Cognitive Dysfunction and Secondary Progressive Disease Course in Multiple Sclerosis

Background and Purpose

The relationship between contingent negative variation (CNV), which is an event-related potential, and cognition in multiple sclerosis (MS) has not been examined previously. The primary objective of the present study was thus to determine the association between CNV and cognition in a sample of MS patients.

Methods

The subjects of this study comprised 66 MS patients [50 with relapsing-remitting MS (RRMS) and 16 with secondary progressive MS (SPMS)] and 40 matched healthy volunteers. A neuropsychological battery was administered to all of the subjects; CNV recordings were made from the Cz, Fz, and Pz electrodes, and the amplitude and area under the curve (AUC) were measured at each electrode.

Results

RRMS patients exhibited CNVs with lower amplitudes and smaller AUCs than the controls at Pz. SPMS patients exhibited CNVs with lower amplitudes and smaller AUCs than the controls, and CNVs with a smaller amplitude than the RRMS patients at both Cz and Pz. After correcting for multiple comparisons, a lower CNV amplitude at Pz was significantly associated with worse performance on measures of speed of information processing, verbal fluency, verbal learning, and verbal recall.

Conclusions

CNV may serve as a marker for disease progression and cognitive dysfunction in MS. Further studies with larger samples and wider electrode coverage are required to fully assess the value of CNV in these areas.     

Lateralized effects of migraine and ANS seizures after closed head injury

Theoretical issues associated with memory, neurocognitive and noradrenergic mechanisms in posttraumatic migraine and dysautonomic complex-partial seizure disorders are reviewed, compared and discussed. Additionally, pretreatment Contingent Negative Variation (CNV) was recorded in a No-GO/GO reaction-time paradigm for 15 normal, and 18 posttraumatic migraine and seizure patients tested not more than three months postinjury. Normals demonstrated that CNV GO and NO-GO responses significantly differed. In both migraine and seizure patients GO and NO-GO trials did not differ significantly. In uncontrolled trials, it was noted that B-Blocker administration increased the difference between GO and NO-GO trials for both migraine and seizure patients over midline leads.     

Preparatory brain potentials in major depressive disorder.

1. Psychomotor slowing in depression is frequently reflected by delayed reaction times (RT). 2. The role of central arousal mechanisms in response slowing was examined by comparing scalp-recorded slow negative potentials of depressed patients with normal controls in two separate studies. 3. Varying fore-warned RT conditions elicited contingent negative variation (CNV) waveforms and the resultant mid-point amplitudes of these waveforms together with orienting (O-wave), expectancy (E-wave) and post-imperative negative variation (PINV) component amplitudes and sensory evoked responses (N1, P2) were compared between groups. 4. RTs were significantly slowed in depressed patients and the patient group exhibited consistently larger PINV amplitudes. Depending on the RT condition, patients also exhibited larger mid-point CNV amplitudes and smaller N1 and P2 amplitudes.     

Vestibular-evoked myogenic potentials in vestibular migraine

Sound-induced vestibular-evoked myogenic potentials (VEMPs) can be used to investigate saccular function, measured from the tonically contracted sternocleidomastoid muscles (SCM) in response to loud sound stimuli. The aim of the present study was to assess VEMPs in patients with vestibular migraine and to determine whether saccular function is affected by the disease. Furthermore, tests such as tilts of subjective visual vertical (SVV) and caloric testing were conducted to test whether deficits in the various tests are associated with each other. The amplitude and latency of VEMPs were measured from the SCM in 63 patients with vestibular migraine (median age 47 years; range 24–70 years) and compared with those of 63 sex- and age-matched healthy controls (median age 46 years; range 17–73 years). Of the 63 patients with vestibular migraine, 43 (68%) had reduced EMG-corrected VEMP amplitudes compared to the controls. Thus, the mean of the p13–n23 amplitudes of the vestibular migraine patients were 1.22 (SE ±0.09) for the right and 1.21 (SE ±0.09) for the left side, whereas the averaged amplitudes of the 63 healthy controls showed a mean of 1.79 (SE ±0.09) on the right and of 1.76 (SE ±0.09) on the left. No difference was seen in the latencies and there was no correlation between VEMP amplitudes, tilts of SVV and caloric testing. Our data on patients with vestibular migraine indicate that the VEMP amplitudes are significantly and bilaterally reduced compared to those of controls. This electrophysiological finding suggests that both peripheral vestibular structures, such as the saccule, but also central vestibular structures are affected. Thus, beside the brainstem, structures in the inner ear also seem to contribute to vertigo in vestibular migraine.     

偏头痛家族聚集性患者临床特点及其一级亲属患病风险因素分析

目的观察偏头痛家族聚集性患者的临床特征,分析其一级亲属的患病风险因素。方法收集资料完整的偏头痛患者72例,根据有无偏头痛家族史分为两组,有偏头痛家族史组及无偏头痛家族史组。利用问卷采集两组患者临床资料,单因素分析筛选出有统计学意义的变量后进行多因素logistic回归分析其一级亲属患病的危险因素。结果 72例中至少有1名一级亲属患有偏头痛者37例,家族史阳性率为51.4%。与家族史阴性的偏头痛先证者比较,家族史阳性的先证者在性别(P=0.675)、年龄(P=0.598)、病程(P=0.419)、先兆(P=0.669)、头痛程度(P=0.837)、发作频率(P=0.465)及头痛伴随症状、头痛部位、头痛性质方面差异无统计学意义;与家族史阴性的头痛先证者比较,家族史阳性的先证者在起病年龄早(16岁)方面的差异(48.6%vs.22.9%,χ~2=5.186,P=0.023)及在头痛发作持续时间长(≥24 h)方面的差异(35.1%vs.14.3%,χ~2=4.170,P=0.041)有统计学意义(P0.05)。多因素回归发现,发病年龄早(OR=2.986,95%CI:1.621~5.503)、头痛发作持续时间长(OR=2.320,95%CI:1.219~4.415)的先证者,其一级亲属患病风险高(P0.05)。结论起病年龄早及头痛持续时间长的偏头痛患者,其一级亲属患偏头痛的风险更高。     

Motor and occipital cortex excitability in migraine patients

OBJECTIVE: We evaluated motor and occipital cortex excitability in migraine patients using transcranial magnetic stimulation. METHODS: In this study, we included 15 migraine patients with aura (MwA), 15 patients without aura (MwoA) between attacks, and 31 normal healthy controls. Motor thresholds at rest, amplitudes of motor evoked potentials, central motor conduction time and cortical silent period were measured by stimulation of the motor cortex by using 13.5 cm circular coil and recording from abductor digiti minimi muscle. Additionally, phosphene production and the threshold of phosphene production was determined by stimulation of the visual cortex with the same coil. RESULTS: No significant differences were observed between the groups with respect to the motor thresholds, Motor evoked potential max/compound muscle action potential max (MEPmax/Mmax) amplitudes, central motor conduction times and duration of cortical silent period. Although not statistically significant, the proportion of the migraineurs with phosphene generation (90%) was found to be higher than that of normal controls (71%). Phosphene threshold levels in migraine patients, however, were significantly lower than those of the controls with MwA patients having the lowest levels. CONCLUSION: Our findings indicate that the occipital cortex, but not the motor cortex, is hyperexcitable in migraine patients.     

Central effects of drugs used in migraine prophylaxis evaluated by visual evoked potentials

The present study used recordings of visual potentials evoked by pattern reversal (VEPs) to investigate the central effects of three drugs used in migraine prophylaxis: the calcium channel blocker nifedipine, the beta-1-selective blocker metoprolol, and the nonselective beta adrenoreceptor blocker propranolol. The study involved 58 patients with common or classical migraine who were treated in a double-blind randomized study over a period of 7 months, while the effectiveness of prophylactic treatment was recorded in headache diaries that were subjected to time series analysis. VEPs were recorded at the beginning of a 2-month baseline period without treatment, after 4 months of treatment, and at the end of a 3-month washout period. At baseline, migraine patients had significantly higher VEP amplitudes and longer latencies than did a group of 87 healthy control subjects. Patients were separated by statistical analysis into responders and nonresponders to each prophylactic treatment. Nifedipine had no effects on the frequency, intensity, and duration of migraine attacks, nor on amplitude and latency of the VEPs. In contrast, the use of beta blockers resulted in a significant decrease in VEP amplitude, both in responders and nonresponders, whereas VEP latency remained unchanged. VEP amplitudes returned to the initial values at follow-up in the nonresponders, but stayed at lower levels in responders. Beta blockers thus appear to have a significant effect on the increased excitability of the visual system in patients with migraine, although their action is not directly related to their reduction of migraine frequency.     

Unilateral cranial autonomic symptoms in patients with migraine

The aim of this study is to investigate the frequency of unilateral cranial autonomic symptoms during migraine attacks, and to compare the clinical characteristics of migraine patients with and without unilateral cranial autonomic symptoms. One hundred and eighty-six consecutive patients with episodic migraine attacks were prospectively included. Cranial autonomic symptoms of the patients occurred during headache, frequency, duration, severity and character of headache, disease duration, presence of aura, laterality of headache, accompanying symptoms, relation of migraine attacks with menstruation, lesions detected on magnetic resonance images, and family history of migraine were recorded. The patients with and without unilateral cranial autonomic symptoms during headache were compared in terms of above-mentioned parameters. Seventy-seven (41.4 %) patients were observed to develop unilateral cranial autonomic symptoms during migraine attack. Disease duration was longer in the patients with unilateral cranial autonomic symptoms than in those without (p = 0.045). Headache was unilateral in 83.1 % of the patients with unilateral cranial autonomic symptoms (p = 0.001). Pure menstrual or menstrually related migraine attacks were more common in the patients with unilateral cranial autonomic symptoms (p = 0.043) and is thought that menstruation-related hormonal factors might have a triggering role on the trigeminal-autonomic reflex pathway. The longer disease duration in patients with unilateral cranial autonomic symptoms might be associated with the activation of pathophysiological mechanisms that cause cranial autonomic symptoms in time. Frequent unilateral pain in migraine patients with unilateral cranial autonomic symptoms is likely to indicate that the development of autonomic symptoms may share common mechanisms with the pathogenesis of trigeminal autonomic cephalalgias.     

Kinesthetic but not visual imagery assists in normalizing the CNV in Parkinson's disease.

OBJECTIVE: This study investigated whether kinesthetic and/or visual imagery could alter the contingent negative variation (CNV) for patients with Parkinson's disease (PD). METHODS: The CNV was recorded in six patients with PD and seven controls before and after a 10min block of imagery. There were two types of imagery employed: kinesthetic and visual, which were evaluated on separate days. RESULTS: The global field power (GFP) of the late CNV did not change after the visual imagery for either group, nor was there a significant difference between the groups. In contrast, kinesthetic imagery resulted in significant group differences pre-, versus post-imagery GFPs, which was not present prior to performing the kinesthetic imagery task. In patients with PD, the CNV amplitudes post-, relative to pre-kinesthetic imagery, increased over the dorsolateral prefrontal regions and decreased in the ipsilateral parietal regions. There were no such changes in controls. CONCLUSIONS: A 10-min session of kinesthetic imagery enhanced the GFP amplitude of the late CNV for patients but not for controls. SIGNIFICANCE: While the study needs to be replicated with a greater number of participants, the results suggest that kinesthetic imagery may be a promising tool for investigations into motor changes, and may potentially be employed therapeutically, in patients with Parkinson's disease.     

Value of the study of contingent negative variation in migraine and tension headache

The aim of this study was to display the result obtained by the contingent negative variation (CNV) recording in patients suffering from headache. Eighty-five patients were taken into account: 59 with migraines (M) and 26 with tension headache (TH). A typical CNV pattern (high CNV amplitude with no habituation) differentiated M from TH. Moreover, psychological data were collected through Rorschach ink blot test among 42 headache sufferers (31 M and 11 TH). The typical Rorschach repressive pattern of alexithymia was found as well in M as in TH while CNV amplitude was significantly higher in the 31 M (-25 microV) than in the 11 TH (-19 microV FP less than 0.04). Biochemical data collected among 28 patients (17 M and 11 TH) revealed a positive correlation between CNV amplitude and plasma level of noradrenaline, regardless of the type of headache (r = 0.58; P less than 0.01). Thus, besides psychological factors, catecholaminergic mechanisms seem implicated in the determination of the CNV pattern in migraine. CNV may help the clinician both to specify diagnosis and to decide between the many therapeutic strategies available.     

Slow cortical potentials in migraine families are associated with psychosocial factors

OBJECTIVE: The aim of the study was the determination of the relationships between neurophysiological and psychosocial factors within the pathogenesis of migraine. METHODS: The contingent negative variation (CNV), parent-child interactions and theirs relationship were investigated in 30 families with a migraine child and 20 healthy families. RESULTS: (1) None of the groups of children, independent of diagnosis, differed according to amplitude or habituation of the CNV. (2) Parents from migraine families exerted significantly more control over migraine children compared with interactions with healthy brothers/sisters. (3) The strong relation between CNV habituation/amplitude and abnormal pattern of parent-child interactions (especially overwhelming dominance and control) was found only for young migraineurs. This relation was not seen in healthy families or for healthy siblings of migraine children. CONCLUSION: This study provides significant evidence for a strong influence of family interactions on the development and maintenance of neurophysiological abnormalities in the migraineous headache. The role of psychosocial factors in the etiopathogenesis of migraine has to be investigated in further studies in more detail.     

Comparison of visual and auditory evoked cortical potentials in migraine patients between attacks.

OBJECTIVE: As both habituation of pattern reversal visual evoked potentials (PR-VEP) (Schoenen J, Wang W, Albert A, Delwaide PJ. Potentiation instead of habituation characterizes visual evoked potentials in migraine patients between attacks. Eur J Neurol 1995;2:115-122) and intensity dependence of auditory evoked cortical potentials (IDAP) (Wang W, Timsit-Berthier M, Schoenen J. Intensity dependence of auditory evoked potentials in migraine: an indication of cortical potentiation and low serotonergic neurotransmission? Neurology 1996;46:1404-1409) were found abnormal in migraine between attacks, we have searched for intraindividual correlations between both tests in 59 migraine patients (22 with aura [MA], 37 without aura [MO]) and in 23 healthy volunteers (HV). METHODS: Amplitude change of the PR-VEP N1-P1 was measured between the 1st and 5th block of 50 sequential averagings during continuous stimulation at 3.1 Hz. IDAP was computed from N1-P2 amplitudes of 100 averagings during stimulations at 40, 50, 60 and 70 dB SL. Amplitude-stimulus intensity function (ASF) slopes and amplitude changes between 40 and 70 dB were calculated. MO and MA differed from HV in PR-VEP amplitude change (P=0.007) and IDAP slope (P = 0.0004). RESULTS: There was no significant correlation between VEP amplitude changes and IDAP slopes, nor between the latter two and attack frequency or disease duration. A negative correlation was found between the amplitude of the first block of averaged responses and potentiation of VEP in all subject groups (P = 0.03) as well as between the amplitude of the auditory evoked potential, at 40 dB, and the percentage of amplitude increase between 40 and 70 dB in MO (P = 0.004) and MA (P = 0.007). ASF slopes and 40 dB amplitudes were significantly correlated only in the MA group (P = 0.002). These results confirm the interictal deficit of habituation in cortical processing of repetitive visual and auditory information in migraine. Since there is no intraindividual correlation between the cortical responses to these sensory modalities they are complementary tools for the study of migraine and may help to identify subgroups of patients with distinct pathophysiological mechanisms. CONCLUSIONS: The strong negative correlation between the initial amplitude of evoked potentials and their amplitude increase during subsequent averaging confirms that the response potentiation in migraine is likely to be due to a reduced preactivation level of sensory cortices.     

Structural brain MRI abnormalities in pediatric patients with migraine

Morphometric MRI studies in adult patients with migraine have consistently demonstrated atrophy of several gray matter (GM) regions involved in pain processing. We explored the regional distribution of GM and white matter (WM) abnormalities in pediatric patients with episodic migraine and their correlations with disease clinical manifestations. Using a 3.0 T scanner, brain T2-weighted and 3D T1-weighted scans were acquired from 12 pediatric migraine patients and 15 age-matched healthy controls. GM and WM volumetric abnormalities were estimated using voxel-based morphometry (p < 0.05, family-wise error corrected). Compared to controls, pediatric migraine patients experienced a significant GM atrophy of several regions of the frontal and temporal lobes which are part of the pain-processing network. They also had an increased volume of the right putamen. The left fusiform gyrus had an increased volume in patients with aura compared to patients without aura and controls, whereas it was significantly atrophied in patients without aura when compared to the other two groups. No abnormalities of WM volume were detected. In migraine patients, regional GM atrophy was not correlated with disease duration and attack frequency, whereas a negative correlation was found between increased volume of the putamen and disease duration (r = ?0.95, p < 0.05). These results show that GM morphometric abnormalities do occur in pediatric patients with migraine. The presence of such abnormalities early in the disease course, and the absence of correlation with patient clinical characteristics suggest that they may represent a phenotypic biomarker of this condition.