Transcranial direct current stimulation of the right temporoparietal junction facilitates hippocampal spatial learning in Alzheimer's disease and mild cognitive impairment.

OBJECTIVE: Spatial memory deficits are an early symptom in Alzheimer's disease (AD), reflecting the neurodegenerative processes in the neuronal navigation network such as in hippocampal and parietal cortical areas. As no effective treatment options are available, neuromodulatory interventions are increasingly evaluated. Against this backdrop, we investigated the neuromodulatory effect of anodal transcranial direct current stimulation (tDCS) on hippocampal place learning in patients with AD or mild cognitive impairment (MCI). METHODS: In this randomized, double-blind, sham-controlled study with a cross-over design anodal tDCS of the right temporoparietal junction (2 mA for 20 min) was applied to 20 patients diagnosed with AD or MCI and in 22 healthy controls while they performed a virtual navigation paradigm testing hippocampal place learning. RESULTS: We show an improved recall performance of hippocampal place learning after anodal tDCS in the patient group compared to sham stimulation but not in the control group. CONCLUSIONS: These results suggest that tDCS can facilitate spatial memory consolidation via stimulating the parietal-hippocampal navigation network in AD and MCI patients. SIGNIFICANCE: Our findings suggest that tDCS of the temporoparietal junction may restore spatial navigation and memory deficits in patients with AD and MCI.

A novel approach to measure brain-to-brain spatial and temporal alignment during positive empathy.

Empathy is defined as the ability to vicariously experience others' suffering (vicarious pain) or feeling their joy (vicarious reward). While most neuroimaging studies have focused on vicarious pain and describe similar neural responses during the observed and the personal negative affective involvement, only initial evidence has been reported for the neural responses to others' rewards and positive empathy. Here, we propose a novel approach, based on the simultaneous recording of multi-subject EEG signals and exploiting the wavelet coherence decomposition to measure the temporal alignment between ERPs in a dyad of interacting subjects. We used the Third-Party Punishment (TPP) paradigm to elicit the personal and vicarious experiences. During a positive experience, we observed the simultaneous presence in both agents of the Late Positive Potential (LPP), an ERP component related to emotion processing, as well as the existence of an inter-subject ERPs synchronization in the related time window. Moreover, the amplitude of the LPP synchronization was modulated by the presence of a human-agent. Finally, the localized brain circuits subtending the ERP-synchronization correspond to key-regions of personal and vicarious reward. Our findings suggest that the temporal and spatial ERPs alignment might be a novel and direct proxy measure of empathy.

Predictors of cardiopulmonary fitness in cancer-affected and -unaffected women with a pathogenic germline variant in the genes BRCA1/2 (LIBRE-1).

Physical activity (PA) helps prevention and aftercare of sporadic breast cancer (BC), cardiopulmonary fitness (CPF) being an age-independent predictor of tumor-specific mortality. Therefore, we wanted to identify predictors of CPF (represented by peak oxygen uptake: VO2peak) in BRCA1/2 mutation carriers whose risk of developing BC is high. We used cross-sectional data from 68 BRCA1/2 germline mutation carrying women participating in the randomized, prospective, controlled clinical study LIBRE-1. Assessments included cardiopulmonary exercise testing, medical and lifestyle history plus socioeconomic status. Additionally, the participants completed a psychological questionnaire regarding their attitude, subjective norms, perceived behavior control and intention towards PA. A multivariate logistic regression model was used to identify predictors for participants reaching their age- and sex-adjusted VO2peak reference values. 22 participants (median age: 40 years, interquartile range (IQR) 33-46) were cancer-unaffected and 46 cancer-affected (median age: 44 years, IQR 35-50). The strongest predictor for reaching the reference VO2peak value was attitude towards PA (Odds Ratio 3.0; 95% Confidence Interval 1.3-8.4; p = 0.021). None of the other predictors showed a significant association. A positive attitude towards PA seems to be associated with VO2peak, which should be considered in developing therapeutic and preventive strategies.Trial registrations: NCT02087592; DRKS00005736.

Multiple-Brain Connectivity During Third Party Punishment: an EEG Hyperscanning Study.

Compassion is a particular form of empathic reaction to harm that befalls others and is accompanied by a desire to alleviate their suffering. This altruistic behavior is often manifested through altruistic punishment, wherein individuals penalize a deprecated human's actions, even if they are directed toward strangers. By adopting a dual approach, we provide empirical evidence that compassion is a multifaceted prosocial behavior and can predict altruistic punishment. In particular, in this multiple-brain connectivity study in an EEG hyperscanning setting, compassion was examined during real-time social interactions in a third-party punishment (TPP) experiment. We observed that specific connectivity patterns were linked to behavioral and psychological intra- and interpersonal factors. Thus, our results suggest that an ecological approach based on simultaneous dual-scanning and multiple-brain connectivity is suitable for analyzing complex social phenomena.

Comparison of three ICA algorithms for ocular artifact removal from TMS-EEG recordings.

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is a powerful tool to investigate brain excitability and information processing in brain networks. However, EEG-TMS recordings are challenging because EEG is contaminated by powerful TMS-related artifacts. Because of these artifacts, different EEG-driven analyses (for instance, source analysis and analysis of information flow on the sensors and source level) reveal incorrect results. The aim of this study was to remove ocular artifacts from TMS-EEG recordings following stimulation of motor cortex using three independent component analysis (ICA) algorithms and to evaluate the effectiveness of these algorithms. We showed that the temporal ICA algorithm better separates those components that contain time-locked eye blink artifacts.

Graph theory in brain-to-brain connectivity: A simulation study and an application to an EEG hyperscanning experiment.

Hyperscanning consists in the simultaneous recording of hemodynamic or neuroelectrical signals from two or more subjects acting in a social context. Well-established methodologies for connectivity estimation have already been adapted to hyperscanning purposes. The extension of graph theory approach to multi-subjects case is still a challenging issue. In the present work we aim to test the ability of the currently used graph theory global indices in describing the properties of a network given by two interacting subjects. The testing was conducted first on surrogate brain-to-brain networks reproducing typical social scenarios and then on real EEG hyperscanning data recorded during a Joint Action task. The results of the simulation study highlighted the ability of all the investigated indexes in modulating their values according to the level of interaction between subjects. However, only global efficiency and path length indexes demonstrated to be sensitive to an asymmetry in the communication between the two subjects. Such results were, then, confirmed by the application on real EEG data. Global efficiency modulated, in fact, their values according to the inter-brain density, assuming higher values in the social condition with respect to the non-social condition.

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.

Migraine in childhood--are periodically occurring migraine attacks related to dynamic changes of cortical information processing?

Amplitudes and habituation of contingent negative variation (CNV) were analyzed in relation to spontaneously occurring migraine attacks in ten children suffering from migraine without aura. Recording took place during feedback training and instrumental conditioning of slow brain potentials. Both the amplitude of the early CNV component and its habituation deficit increase during the 5 days prior to a migraine attack, with maximum abnormalities the day before the ictal episode. Abrupt reduction of the amplitude and normalization of the CNV habituation were observed during the attack. This study provides evidence for neurophysiological periodicity in young migraineurs and emphasizes that the time relative to the migraine attacks must be considered in studies of juvenile migraine during the headache-free period.

Migraine--evidence for a disturbance of cerebral maturation in man?

The contingent negative variation (CNV), a slow cortical potential between two defined stimuli, was used to record the effect of age in 162 migraine patients and 320 healthy controls aged between 8 and 59 years. The early component (iCNV) and habituation slope of 32 GO-trials are presented. There were no significant differences between healthy controls and migraine patients in iCNV amplitudes or habituation slope up to the age of 19 years. In the age groups from 20-59 years the healthy controls showed a significantly reduced iCNV compared with migraine patients and healthy controls below 20 years of age. While the habituation slope increased in healthy controls, there was no habituation of iCNV in migraine patients. It is suggested that reduced iCNV amplitudes in healthy controls indicate a state of cerebral maturation. This maturation effect is missing in adult migraine patients, leading to pronounced attentional effort in these patients.

Contingent negative variation as indicator of duration of migraine disease.

Amplitudes of early wave contingent negative variation (iCNV) reveal significant differences between migraine patients and healthy controls, indicating a lack of habituation and pronounced attentional functions in migraine patients. CNV amplitudes were recorded in 20 migraine patients. The CNV amplitudes were Pearson correlated with the individual duration of the migraine disease. Only iCNV correlates inversely with the duration (r = -.544). The data show an influence of duration of migraine disease on iCNV amplitudes. It is suggested that iCNV is an indicator of chronicity in persistent migraine.

Clinical efficacy and central mechanisms of cyclandelate in migraine: a double-blind placebo-controlled study.

The mechanisms of action of calcium antagonists in the prophylactic treatment of migraine remain unclear. The most likely proposed mechanism seems to be via influence on the central nervous system, but the central effects of calcium entry blockers are insufficiently characterized. The aim of the present study was to investigate the central mechanisms behind the efficacy of cyclandelate in a double-blind placebo-controlled parallel-designed study using the contingent negative variation (CNV), an event-related slow potential for measuring cortical excitability and investigating preparation processes. The CNV recordings were performed in 25 females suffering from migraine without aura before treatment (baseline), after single dose administration of cyclandelate or placebo and after 8 weeks' treatment with cyclandelate (cyclandelate group, no.=15) or placebo (placebo group, no.=10). Cyclandelate reduced significantly the days with migraine and duration of migraine compared to placebo. In the cyclandelate group a significant reduction of all CNV components was observed and the changes in amplitudes compared to baseline were more pronounced after treatment. Placebo reduced the late CNV component only after single dose administration. There were no changes in the early and total CNV. Cyclandelate did not normalize the habituation of the slow negative potential. The results are discussed in terms of the influence of cyclandelate on cortical excitability and of the prevention of cortical spreading depression via antagonistic effect on calcium channels.

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.

[Compulsive phenomena in children with tic disorder and attention deficit-hyperactive disorder]. / Zwangsphänomene bei Kindern mit Tic-Störung bzw. Aufmerksamkeitsdefizit-Hyperaktivitätsstörung.

Tic disorders (TD), obsessive-compulsive disorders (OCD) and attention-deficit/hyperactivity disorder (ADHD) are often associated with deficits of impulse control and aggressive behavior. Tic disorders and OCD are closely related on epidemiological, psychopathological and neurobiological levels, whereas ADHD and OCD phenomena seem to be at opposite poles. Research evidence on the clinical significance of associated obsessive-compulsive behavior is reviewed and linked to our own new data. Thus the analyses of a worldwide database on Tourette's Syndrome (TS) (N = 4,833) showed that that the associated symptomatology of the OCD spectrum has to emphasized. In further investigations, premonitory sensorimotor phenomena reminiscent of OCD were more frequent in children with tic disorders as they grew older. Obsessive-compulsive behavior concomitant with TS was particularly associated with impulsive and aggressive behavior, as well as with depression and anxiety. The data suggest a reduced serotonergic transmission. Self-reports by children with ADHD, as opposed to those by their parents, mentioned a significantly higher quantitative degree of OC phenomena than those by children with TS. These findings suggest that OC symptoms in children with ADHD have so far been neglected in assessments by others. In summary, a complex psychopathological pattern of tic, OC behavior, impulsivity and internalizing symptomatology emerges that requires discriminating assessment and treatment.

Investigating the neural basis of cooperative joint action. An EEG hyperscanning study.

The aim of the present study is to investigate the neurophysiological basis of the cognitive functions underlying the execution of joint actions, by means of the recent technique called hyperscanning. Neuroelectrical hyperscanning is based on the simultaneous recording of brain activity from multiple subjects and includes the analysis of the functional relation between the brain activity of all the interacting individuals. We recorded simultaneous high density electroencephalography (hdEEG) from 16 pairs of subjects involved in a computerized joint action paradigm, with controlled levels of cooperation. Results of cortical connectivity analysis returned significant differences, in terms of inter-brain functional causal links, between the condition of cooperative joint action and a condition in which the subjects were told they were interacting with a PC, while actually interacting with another human subject. Such differences, described by selected brain connectivity indices, point toward an integration between the two subjects' brain activity in the cooperative condition, with respect to control conditions.

Neuroimaging and neurogenetics of epilepsy in humans.

In the past decade, several genetic mutations have been associated with different forms of familial focal and generalized epilepsies. Most of these genes encode ion-channel subunits. Based on neurophysiological in vitro and in vivo animal studies, substantial progress has been made in understanding the functional consequences of gene defects associated with epilepsies. However, the knowledge transition from animal studies to patients carrying a mutation, or even suffering from a nonfamilial form of epilepsy, is very limited. This review will illustrate how neuroimaging studies in humans may help to bridge the gap between genotype and phenotype. We will be presenting examples of familial focal (autosomal dominant nocturnal frontal lobe epilepsy), idiopathic generalized epilepsies (severe myoclonic epilepsy of infancy). Such studies will help to better understand functional consequences of genetic alterations and may contribute to a better phenotype characterization.

Central mechanisms of controlled-release metoprolol in migraine: a double-blind, placebo-controlled study.

beta-Blockers are widely used in the prophylaxis of migraine and have been described as very effective drugs in many studies. Some investigators have demonstrated that the clinical improvement of migraine corresponds to the normalization of the contingent negative variation (CNV), a slow cortical potential measuring cortical information processing. However, most of these studies have contained a variety of methodological pitfalls, which we attempted to address in the current study. Twenty patients suffering from migraine without aura were randomly divided into two groups. The groups were treated either with controlled-release metoprolol or placebo for 3 months, using a double-blind design. Twice before and once after each month of the treatment the CNV was recorded. After 3 months, a significant reduction of migraine frequency, duration and intensity was demonstrated for the metoprolol compared with the placebo group. The CNV was characterized by a marked reduction of the amplitude of the total CNV and postimperative negative variation and normalization of the eartly CNV habituation following treatment. Therefore, metoprolol may exert its prophylactic effect in migraine through the influence on cortical information processing and excitability represented by the CNV.

Relationship between precipitating agents and neurophysiological abnormalities in migraine.

The particular mechanisms of migraine anticipation by different precipitating agents are still unknown. The contingent negative variation (CNV) was recorded in the premenstrual and ovulation phases of the cycle in both rest and stress conditions in 17 migraine and 15 healthy women. In migraineurs a significant increase of amplitude of the initial CNV component in the premenstrual phase compared with ovulation was observed. During both the ovulation and premenstrual phases both migraineurs and controls demonstrated a significant increase of the CNV amplitude on stress. The increase of the amplitude on stress in the premenstrual phase was more pronounced in migraineurs. This study shows that stress and menstrual cycle are associated with changes of the initial CNV amplitude, probably indicating a higher probability of migraine attacks.

Coping styles of headache sufferers.

Psychological factors are important in the chronification and aggravation of headaches. We studied 90 patients suffering from migraine, chronic daily headache (CDH) evolved from migraine, and episodic or chronic tension-type headache (TTH). Emotional, cognitive, and behavioral pain coping were assessed using the Kiel Pain Inventory (KPI), Beck's Depression Inventory, the State-Trait-Anxiety Inventory, and Quality of Life Questionnaire. In addition, the clinical course of headache was analyzed using a validated headache diary. The results were as follows. Firstly, the KPI is reliable internally for the assessment of pain-coping strategy employment among headache patients. Secondly, migraine sufferers were characterized by pronounced psychological abnormalities during the headache phase, demonstrating a less adaptive coping behavior. This was in contrast to the TTH patients, who showed more general distress manifesting in elevated anxiety and lower quality of life. The only factor which appeared to be essential for differentiating between migraine and TTH was the intensity of headache. Thirdly, chronic TTH and CDH evolved from migraine demonstrated more pronounced psychological disabilities and more severe clinical courses of headaches than episodic TTH or nontransformed migraine. The predictor variable for transformation of migraine was impairment of well-being/quality of life, and for transformation of TTH, the frequency of headaches and depression. Finally, analgesic misuse seems to be less important for chronification and transformation of headaches than the degree of psychological disability. This study draws attention to the role of psychological factors in the chronification of TTH and transformation of migraine and provides some recommendations for the behavioral treatment of chronic headaches.

Neurofeedback--the significance of reinforcement and the search for an appropriate strategy for the success of self-regulation.

Nine healthy children took part in five sessions of feedback and instrumental conditioning of slow cortical potentials (SCPs). The feedback conditions (the relation between the feedback signal and amplitude of SCP) were inverted after two sessions. Neither the children nor the therapists were aware of this change. The adjustment of the children to the new feedback setting and the self-regulation strategies employed were investigated. The results were as follows: (a) Healthy children achieved control over cortical negativity within two sessions. (b) The change of feedback conditions worsened the regulation abilities, which then improved again within the following three sessions. (c) After the first two sessions, the participants were able to describe strategies that were successful during different phases of self-regulation. (d) Following the change in the feedback conditions, the children reevaluated the way they influenced their SCPs. However, they did not alter the cognitive or behavioral strategies. The study demonstrated that positive and negative reinforcement and the knowledge of results are more important for successful self-regulation than the search for effective strategies. The relevance of these findings is discussed.

What kind of habituation is impaired in migraine patients?

The acoustically evoked cortical potentials of 20 migraine patients were investigated using a combined conditioning-testing and oddball paradigm. The short- and long-term habituation results of the P50 and P300 waves were compared with 16 healthy subjects. Migraineurs were characterized by a sensory gating deficit of the P50 wave (reduced short-term habituation) in the non-target condition and a reduced long-term habituation of the P300 wave in the target condition. The study describes disturbances of information processing on the automatic and cognitive levels in migraine patients and emphasizes the role of sensory gating and orienting response in migraine pathogenesis.