Prenatal maternal distress seems to be associated with the infant's temperament and motor development: an explorative study.

According to the concept of fetal programming, prenatal distress has long-lasting consequences on the offspring's health later in life. The hypothalamic-pituitary-adrenal axis is considered a mediating system by which maternal distress is transferred to the fetus in intrauterine environment. In this longitudinal explorative study on 30 mother-child-dyads, reported maternal distress and salivary cortisol were collected during pregnancy. Infant temperament, motor and cognitive development were assessed at 16 months. Additionally, infant cortisol levels throughout the day and in reaction to a psycho-social stressor where measured. As expected, infants whose mothers had experienced higher prenatal distress expressed a more difficult temperament and lower fine motor development at 16 months. No association could be shown between prenatal maternal distress and infant salivary cortisol.

No deficit in neurocortical information processing in patients with cleft lip and palate.

BACKGROUND: Cleft lip and palate (CLP) represents the most common malformation of the midfacial region worldwide. It can be suggested that the facial stigmatization, the speech impediment, and the long-standing pressure of treatment cause a range of life stressors. Neurocortical information is influenced by physiological and psychological factors and varies significantly in patients suffering from chronic stress, anxiety, depression, or other psychopathological conditions following maladaptation. The aims of the present study were to investigate the neurocortical information processing of patients with CLP using the contingent negative variation (CNV) paradigm and to evaluate secondary psychopathology, anxiety, and depression. MATERIALS AND METHODS: Twenty-five adults with CLP and 25 healthy volunteers, matched in age and gender, were investigated using recordings of the CNV. Initial CNV (iCNV), late CNV (lCNV), and total CNV (tCNV) as well as habituation slope of the iCNV were determined in each subject. Additionally, each participant had to complete the hospital anxiety and depression questionnaire (HADS) and the Symptom Checklist-90-R (SCL-90-R). RESULTS: Individuals with CLP did not differ significantly from healthy subjects according to any of the CNV parameters investigated. No correlations could be revealed between the measured items and the confounding factors age and gender. Additionally, there were no differences between the groups regarding depression and SCL-90-R; however, anxiety showed significant group differences on a subclinical level. CONCLUSIONS: These data suggest that subjects with CLP show normal neurocortical information processing. It seems likely that CLP and its treatment have no impact on psychosocial functioning and neurophysiological mechanisms of attention. CLINICAL RELEVANCE: The specific living conditions of patients with CLP do not result in disease-specific neurophysiological changes.

Disease duration of episodic migraine correlates with modified amplitudes and habituation of contingent negative variation.

Cortical habituation in episodic migraine patients without medication overuse headache (MOH), recorded by contingent negative variation (CNV), is often reduced compared with healthy controls. There is evidence that with longer duration of migraine disease (DOD) amplitudes and habituation of CNV become progressively abnormal. The aim of the study was to examine habituation characteristics of contingent negative variation in episodic migraine patients suffering from short- and long-lasting migraine compared to matched healthy controls. 32 migraine patients without aura and without MOH diagnosed according to the revised ICHD-II criteria and 16 age- and sex-matched healthy controls were included. According to DOD, the total sample of migraine patients was divided into two groups (group a: DOD <121 months, n = 17 subjects, group b: DOD >120 months, n = 15 subjects). Both migraine groups did not differ in the number of days of migraine and the duration of attacks. Overall CNV and initial CNV differed significantly between migraine patients and controls, whereas the former produced more negative amplitudes. In the migraine group lack of or deficient habituation occurred, whilst controls showed habituation. There were middle range correlations between the DOD and overall CNV, initial CNV, and y-intercept. Patients suffering from long-lasting migraine produced higher CNV amplitudes with a higher y-intercept. The results are interpreted as "maladaptive plasticity" with a risen intercept in long-lasting migraine.

Does an aerobic endurance programme have an influence on information processing in migraineurs?

BACKGROUND: Migraine is a disorder of central information processing which is characterized by a reduced habituation of event-related potentials. There might be positive effects of aerobic exercise on brain function and pain. The aim of this study was to investigate the influence of exercise on information processing and clinical course of migraine. METHODS: 33 patients completed a ten-week aerobic exercise programme. To examine the influence of the treatment on information processing and attention, Trail Making Test (TMT) A and B, d2-Letter Cancellation Test (LCT) and recordings of the Contingent Negative Variation (CNV) were performed before and after the training. RESULTS: Patients showed a significant reduction of the migraine attack frequency, the iCNV-amplitude and the processing time for TMT-A and TMT-B after treatment. Moreover, there was a significant increase of the habituation and positive changes in parameters of attention (d2-LCT) after the training. CONCLUSIONS: This study demonstrates that aerobic exercise programme influences central information processing and leads to clinical effects on the migraine symptomatology. The results can be interpreted in terms of an improvement of a dysfunctional information processing and a stimulus selection under aerobic exercise.

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.

Behavioural treatment increases activity in the cognitive neuronal networks in children with attention deficit/hyperactivity disorder.

Response cost and token approach (RCT) within the scope of a summer camp training is an effective treatment program for attention deficit hyperactivity disorder (ADHD). It is likely that intensive RCT training influences networks responsible for ADHD symptoms. Functional magnetic resonance imaging (fMRI) was carried out in 12 children with ADHD before and after the RCT program and in 12 healthy control children twice. For fMRI, a Go/No-go paradigm was used to investigate the influence of RCT training on attention and impulsivity. The No-go condition revealed only weak activation in the dorsal part of the anterior cingulate cortex (ACC), parietal and dorsolateral prefrontal cortex (DLPFC) before the training in children with ADHD compared to healthy children. However, this activation in these brain regions was significantly more pronounced after the training. This increase in hemodynamic response cannot be attributed merely to repetition of the measurement since the effect was not observed in healthy children. The increase in hemodynamic response in the ACC and right DLPFC was significantly associated with a reduction in response time variability and clinical symptoms in ADHD patients. After the RCT training, the children with ADHD demonstrated more pronounced activation of cortical structures which are typically related to response monitoring and self-control. It seems likely that children with ADHD learned more cognitive control in a continuous performance task as was revealed by both neuropsychological outcome and fMRI.

Cortical habituation deficit in tinnitus sufferers: contingent negative variation as an indicator of duration of the disease.

Cortical attention and habituation parameters are altered in patients suffering from tinnitus. The aim of the study was to quantify cortical attention and habituation parameters in tinnitus patients by recording the contingent negative variation (CNV) response and to correlate amplitudes of different CNV parameters with duration of disease. Twenty patients suffering from tinnitus (median: 44 years) and twenty age- and sex-matched healthy controls (median: 41 years) were tested by a CNV paradigm. We recorded overall CNV, initial CNV, and terminal CNV and calculated habituation slopes. All CNV parameters were Spearman-correlated with individual duration of disease. Highly significant between groups differences emerged in total (tinnitus: -8.4 uV vs. controls: -3.8 uV), initial (-11.2 vs. -6.0 uV), and terminal CNV (-11.9 vs. -6.5 uV) demonstrating higher negative amplitudes in tinnitus patients. Habituation differed in total and terminal CNV, indicating missing habituation in tinnitus patients. Overall CNV (ϱ = -.365) and initial CNV (ϱ = -.529) showed a medium Spearman correlation with duration of disease. We conclude that the correlation between duration of tinnitus and the initial CNV amplitudes indicates an altered state of cortical excitability that can also be observed in more negative CNV-amplitudes in tinnitus patients. We assume that this state indicates a chronicity process in tinnitus disease.

Does inert gas narcosis have an influence on perception of pain?

The effect of an increased nitrogen partial pressure under hyperbaric conditions is known as nitrogen narcosis (NN). At an ambient pressure of about 4 bar, reduced cognitive performance as well as euphoric effects are reported. We examined the effect of NN on pain perception. 22 subjects completed an experimental (50 meters = 6 bar) and a simulated control dive (0 m = 1 bar) in a hyperbaric chamber. Before and during each dive a standardized cold pressure test was performed. The intensity of pain perceived was assessed with the help of a visual analogue scale; additionally, subjects assessed the subjective effect of NN. The study showed that the perceived pain intensity is significantly reduced under nitrogen narcosis conditions (F1.21 = 5.167, p < 0.034) when compared to the perceived pain intensity under the control dive conditions (F1.21 = 0.836, p = 0.371). A connection between perceived pain intensity and subjects experience of the NN was not found under the experimental dive condition (r = 0.287, p = 0.195). We could show that even relatively moderate hyperbaric conditions may have an influence on the perception of pain. The results are highly relevant since nitrogen narcosis occurs in divers as well as in medical personnel or construction workers, working under hyperbaric conditions.

Behavioural treatment programme contributes to normalization of contingent negative variation in children with migraine.

BACKGROUND: Migraine is a disorder of central information processing which may be characterized by increased amplitudes and reduced habituation of evoked and event-related potentials. In this pilot study, special behavioural training of habituation to aversive stimuli (MIPAS-Family = Migraine Patient Seminar for Families) was developed and proven effective in children suffering from migraine without aura. METHODS: 13 children with migraine participated in the MIPAS-Family programme and 13 other children with migraine were treated with biofeedback. The influence of both treatments on abnormal cortical information processing in migraine was assessed using recordings of the contingent negative variation (CNV), an event-related slow cortical potential. RESULTS: Both MIPAS training and biofeedback caused an equal reduction of migraine frequency and severity. However, MIPAS treatment was associated with a significant increase in iCNV habituation. Changes in the clinical course of migraine correlated positively with normalization of habituation: the greater the reduction in headache frequency, the greater the increase in CNV habituation was. These effects were not observed in the biofeedback group. CONCLUSIONS: This study demonstrates that the specific treatment programme which was evolved from knowledge of pathogenetic mechanisms of migraine influences central information processing and leads to a clinical effect.

Component-specific self-regulation of slow cortical potentials and its effect on behavior: an exploratory study.

In the present study, the possibility of component-specific self-regulation of the contingent negative variation (CNV) and the functional significance of the iCNV (initial or early CNV component) and tCNV (terminal or late CNV component) were investigated in twenty-four healthy volunteers. The subjects were able to achieve control over a particular CNV component within four sessions. Regulation of the tCNV was more successful than for the iCNV. Specific control over iCNV was associated with strategies mainly related to the pre-stimulus interval or the warning stimulus (S1), while regulation of the tCNV was assigned to activities during the whole interstimulus interval or around the imperative stimulus (S2). It can be concluded that component-specific regulation of the CNV can be used in studies of the psychophysiological meaning of this potential, representing different stages of information processing. The role of cortical pre-activation in the generation of the iCNV and the phasic performance-directed activation of the tCNV can be hypothesized.

Neuropsychological deficits in scuba divers: an exploratory investigation.

OBJECTIVE: To investigate whether divers with varying levels of experience and without a history of reported decompression sickness (DCS) show neuropsychometric alterations possibly as a result of so-called repetitive "silent" paradoxical gas embolisms. METHODS: Using reaction time as a psychometric measure, 17 experienced military divers (ED, logging between 150 and 1,200 diving hours) and eight very experienced military divers (VED, logging between 2,800 and 9,800 diving hours) with no decompression sickness (DCS) in their medical histories were compared to 23 healthy controls without any diving history, matched as closely as possible with respect to age for the two diving groups. Motor reaction time, decision reaction time and error rates were measured during completion of both simple and complex reaction time tasks. RESULTS: Compared to their control group, VED showed significantly higher motor reaction times on both tasks and significantly higher decision reaction times in the complex task. ED were not found to be different from their respective controls. No changes in performance quality in terms of increased errors were observed in any of the tasks for either diving group. CONCLUSIONS: The findings support the proposed possibility that minimal cerebral lesions occur after diving even without DCS. Further studies with this highly selective population of very experienced divers using more elaborate neurocognitive and neuromotor tasks seem warranted.

Developmental changes of the contingent negative variation in migraine and healthy children.

It has been hypothesized that abnormalities of information processing in migraine may be attributed to impairment of cerebral maturation. However, the most evidences for this hypothesis have come from cross-sectional studies during childhood. We performed a longitudinal study and recorded contingent negative variation (CNV), an event-related slow cortical potential, in migraine children (n = 27) and age-matched healthy individuals (n = 23) in 1998 and 8 years later (2006). Amplitudes of all CNV components were reduced and habituation of the initial CNV (iCNV) increased in the observed time. However, the reduction of the iCNV amplitude was more pronounced in migraine patients who were in remission in 2006 and in healthy subjects and less pronounced in migraineurs with persisting headaches. Patients with the worsened migraine demonstrated the most pronounced loss of iCNV habituation in 1998 and significantly increased iCNV amplitudes in 2006. This longitudinal study supports the hypothesis of impaired cerebral maturation in migraine and shows that migraine manifestation is a key factor interfering with the natural maturation process of central information processing.

MIPAS-Family-evaluation of a new multi-modal behavioral training program for pediatric headaches: clinical effects and the impact on quality of life.

Several meta-analyses have demonstrated that the combination of electrical muscle activity and Temperature Biofeedback could be regarded as gold standard in chronic pediatric headaches. However, these techniques seem to be uneconomical and furthermore they are not directed to improve the social competence as well as resolve possible impairments in daily activities of the child. Therefore, multi-modal behavioral techniques have been proposed, but no studies comparing these with the gold standard were conducted. The present study compared the impact of a new multi-modal behavioral education and training program--MIPAS-Family--with a combined Biofeedback treatment, evaluating clinical efficacy as well as the effect on the quality of life (QoL) of children with chronic headaches. Thirty-four children and adolescents with recurrent headache, ranging from 7 to 16 years, were randomly assigned to the MIPAS-Family (N = 19) or the Biofeedback (N = 15) condition. All patients were diagnosed by the criteria of the International Headache Society. The children and their parents completed headache diaries, diaries of daily living activities and a QoL questionnaire (KINDL). Both groups showed significant improvements concerning the headache intensity and headache duration. We found no significant differences in the main headache parameters between both treatments. After the treatments, the children were less disturbed by their headaches in the domains school, homework, and leisure time. In conclusion, MIPAS-Family is as effective as Biofeedback but it is more cost-effective and addresses the whole family and the daily activities.

Contingent negative variation in acute trauma patients: A prospective exploratory study.

It is still unclear why some individuals completely recover after an acute trauma and others develop a long-lasting post-traumatic stress disorder (PTSD). This study investigates whether the contingent negative variation (CNV) - a slow negative event-related potential - may be associated with the occurrence of PTSD after acute trauma. CNV (auditory 2-stimulus reaction time paradigm) was recorded within one month as well as 6 months after an acute trauma (dangerous or grave physical injuries, witnessing of attempted suicide or murder, robbery, extortion, accidents, heavy illness, death or loss of an important person, hostage-taking) in 39 otherwise healthy adults and compared with CNV recordings in 38 healthy control subjects without potentially traumatizing experience in their history. According to their subsequent clinical course, these subjects were divided into two groups: participants who recovered completely 1 month after the trauma (PTSD- group, n = 31), and those who began to experience PTSD (PTSD+ group, n = 8). Patients from both trauma groups were characterized by a significantly longer reaction time immediately after the trauma. The PTSD+ group demonstrated lower amplitudes of the late CNV component immediately and six months after the trauma compared with the PTSD- and the control group. Whether the lower CNV amplitudes in patients who develop PTSD after the acute trauma, which is already present in the first days after the trauma, may be related to a higher risk for development of PTSD in these subjects, this has to be clarified in further prospective studies.

Neurophysiological reactivity before a migraine attack.

Migraine patients are characterized by increased amplitudes and reduced habituation of the contingent negative variation (CNV) response, especially before a migraine attack. As shown previously, migraine provoking and precipitating agents can cause CNV abnormalities. However, it is unclear whether the temporal relation to the migraine attack determines how the brain reacts to a migraine precipitant. In this study, experimentally-induced achievement stress, one of the typical precipitants for migraine, was examined for its effects upon the CNV response. CNV was recorded during conditions of rest and stress, both before and after a migraine attack, as well as during a headache-free interval. The neurophysiological reactivity to stress in migraineurs was compared with those of healthy subjects. Before a migraine attack, migraine patients demonstrated significantly more pronounced neurophysiological reactivity to stress: the amplitude of the early CNV component was more increased and its habituation was more reduced in the stress condition, especially 1-3 days before an attack compared with changes of CNV amplitudes and habituation under stress obtained after an attack, during the headache-free interval, or in healthy controls. The study demonstrates that the brain of migraine patients is characterized by increased susceptibility to migraine provoking agents before an actual attack.

Lifestyle intervention in BRCA1/2 mutation carriers: study protocol for a prospective, randomized, controlled clinical feasibility trial (LIBRE-1 study).

BACKGROUND: Women with highly penetrant BRCA mutations have a 55-60% lifetime risk for breast cancer and a 16-59% lifetime risk for ovarian cancer. However, penetrance differs interindividually, indicating that environmental and behavioral factors may modify this risk. These include lifestyle factors such as physical activity status, dietary habits, and body weight. The modification of penetrance by changing lifestyle factors has not thus far been investigated in a randomized trial in BRCA mutation carriers. METHODS: Therefore, we intend to enroll 60 BRCA1/2 mutation carriers in a pilot feasibility study (Lifestyle Intervention Study in Women with Hereditary Breast and Ovarian Cancer (LIBRE) pilot). This multi-center, prospective, controlled trial aims to randomize (1:1) participants into a (1) multi-factorial lifestyle intervention group (IG) versus (2) the control group with usual care (CG). The primary endpoint is feasibility and acceptance of a structured interdisciplinary lifestyle intervention program over 12 months (at least 70% of the patients to complete the 1-year intervention). Furthermore, the effects on physical fitness, BMI, quality of life, and stress coping capacity will be investigated. During the first 3 months, women in the IG will receive structured, individualized and mainly supervised endurance training of ≥18 MET*h/week (MET = metabolic equivalent task) and personal nutritional counseling based on the Mediterranean diet. During the subsequent 9 months, the IG will receive monthly group training sessions and regular telephone contacts for motivation, whereas the CG will only receive usual care (one general counseling on healthy nutrition and benefits of regular physical activity on health status). At randomization and subsequent time points (3, 6, 12 months), cardiopulmonary fitness will be assessed by spiroergometry and nutritional and psychological status by validated questionnaires. DISCUSSION: This pilot study will investigate the optimal strategy to improve physical fitness, nutritional habits, and psychological factors in women at high risk for developing breast or ovarian cancer. The results of this pilot feasibility study will be the basis for a larger prospective randomized trial including clinical events (LIBRE). TRIAL REGISTRATION: ClinicalTrials.gov, NCT02087592.

Slow cortical potentials in migraine. Predictive value and possible novel therapeutic strategies to prevent an attack.

During the pain-free interval migraine patients display increased negative amplitudes in recordings of slow cortical potentials compared to healthy controls. This fact can be linked to diminished or absent habituation during the recording session. This difference in amplitude and habituation is at its maximum the day before the migraine attack. After the attack, amplitudes and habituation course are comparable with those of healthy controls. This observation enables the migraine patient to predict the next migraine attack and to become acquainted with other symptoms which indicate an imminent attack and which can be present one or two days before it. During this period, when the attack has begun but the pain has not yet developed, novel therapeutic strategies for preventing the full-blown attack can be introduced. These "pre-emptive" strategies--which may include intake of tranquillizers to reduce the high cortical arousal, but also non-medical relaxation methods--constitute neither acute treatment (because there is no acute pain) nor prophylaxis.

Contingent negative variation in subjects at risk for migraine without aura.

Migraine is a complex disease with a significant genetic background. One possible strategy to investigate the genetics of migraine is the evaluation of functional vulnerability markers or biological elementary endophenotypes in individuals with the greatest probability of developing the disorder (high-risk design). In this study the contingent negative variation (CNV) was recorded in 35 high-risk subjects with a positive family history of migraine without aura (FHP), 35 low-risk individuals without a positive family history (FHN), and 35 migraineurs (migraine without aura). FHP subjects and migraine patients differed significantly from FHN individuals with regard to amplitude and habituation slope of the early CNV component (initial CNV or iCNV). FHP participants demonstrated the same iCNV abnormalities and distribution among iCNV characteristics as migraineurs. The amplitude of the iCNV correlated significantly with the relative number of subjects suffering from migraine among first- and second-degree relatives. The higher the density of affected individuals in the family, the more pronounced were the CNV abnormalities in relatives. This study provides evidence that the familial factor contributes to the abnormal amplitude, and to a lesser degree, habituation of the iCNV, and that the iCNV may be used as a functional-genetic vulnerability marker in further research of migraine genetics.

Changes in cortical dynamics in the preictal stage of a migraine attack.

Neurophysiologic studies suggest that migraineurs without aura have a dysfunction of cortical information processing in the pain-free interval. In this study, the advanced method of nonlinear multielectrode sleep-EEG analysis is used to investigate changes of cortical activity in the preictal time span. Five patients (four women, one man; age range, 29 to 58 years) experiencing migraine without aura participated in the study. The patients spent two blocks in the sleep laboratory. The first block was taken in a headache-free interictal time interval, and the second block when the onset of a migraine attack was most likely. After a nocturnal migraine attack, the patient was asked to mark the maximum of migraine pain in a surface-head scheme. The comparison of preictal and interictal EEGs enabled the authors to obtain a topographical view of changes in cortical dynamics. In each patient map, an area was found that displayed a pronounced focus indicating the region of maximum change in dimensional complexity. It shows a clearly recognizable correspondence with the scalp topography of the later pain perception. These findings indicate an association between cortical status and pain lateralization in the preictal time span.

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.