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.

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.

Migraine and asthma in childhood: evidence for specific asymmetric parent-child interactions in migraine and asthma families.

In spite of the fact that migraine often manifests as a familial disorder, the role of the family in migraine has not been adequately explored. In this study parent-child interactions in 20 families with a child suffering from migraine were analysed and compared with 20 healthy families and 20 families with an asthma child. The families had to solve a puzzle within a limited time. Parent-child interactions within migraine and asthma families were asymmetric, revealing a disease-specific interpersonal context in the family. Communication with the affected child in migraine families was significantly more directive, with more specific instructions and less help, towards migraineurs than with the healthy siblings. Dominance of parents and submissive behaviour of children were the main features of interactions. In asthma families interactions were more conflicting and less cooperative. This study demonstrated a specific, asymmetric, pattern of family interactions predisposing children either to migraine or asthma.

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.

[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.

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.

Self-regulation of slow cortical potentials in children with migraine: an exploratory study.

Migraine patients are characterized by increased amplitudes of slow cortical potentials (SCPs), representing pronounced excitability of cortical networks. The present study investigated the efficiency of biofeedback training of SCPs in young migraineurs. Ten children suffering from migraine without aura participated in 10 feedback sessions. They were compared with 10 healthy children for regulation abilities of cortical negativity and with 10 migraineurs from the waiting list for clinical efficacy. During the first two sessions, the migraine children were characterised by lacking ability to control cortical negativity, especially during transfer trials, compared with healthy controls. However, there was no difference following 10 sessions of training. Feedback training was accompanied by significant reduction of cortical excitability. This was probably responsible for the clinical efficacy of the training; a significant reduction of days with migraine and other headache parameters was observed. It is suggested that normalization of the threshold regulation of cortical excitability during feedback training may result in clinical improvement.

Are the periodic changes of neurophysiological parameters during the pain-free interval in migraine related to abnormal orienting activity?

OBJECTIVE AND METHODS: Migraine patients are characterized by increased amplitude and reduced habituation of contingent negative variation (CNV). Furthermore, the CNV underlies periodic changes during the pain-free interval, being maximal before attack. The periodicity of CNV is related to periodic changes in habituation, probably due to variation of orienting activity during the pain-free interval. CNV and orienting response (OR) were studied in 20 females suffering from migraine without aura and in 12 matched healthy females. The neurophysiological recordings in the group of patients were performed 1-4 days before and 4 days after a migraine attack. The amplitudes and habituation of early and late components and total CNV were calculated. The OR was assessed using the habituation of the skin conductance response (SCR) and alpha blocking (AB). The non-parametric tests were employed for statistical analysis. RESULTS: There were no differences between the two groups for habituation of all CNV components and of SCR following an attack. However, the habituation of AB was significantly reduced in migraine. Before attack we observed a significantly reduced habituation of the early and total CNV and of the AB compared to controls and recordings performed after an attack. The habituation of the late component and of SCR remained unchanged. CONCLUSIONS: The abnormal habituation could be explained by the periodic changes of physiological parameters during the pain-free interval. The impaired habituation of early CNV in migraine is associated with increased orienting activity seen only in the central component (AB) of OR.

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.

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.

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.

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.