The effectiveness of three mobile-based psychological interventions in reducing psychological distress and preventing stress-related changes in the psycho-neuro-endocrine-immune network in breast cancer survivors: Study protocol for a randomised controlled trial.

Background: A growing body of literature shows that psychological distress is not only a major threat to psychological well-being but can also have a significant impact on physical health. In cancer patients, it can negatively affect prognosis and posttreatment recovery processes. Since face-to-face psychological interventions are often inaccessible to cancer patients, researchers have recently been focusing on the effectiveness of eHealth adaptations of well-established approaches. In this context, there has been a call for high-quality randomised controlled trials that would allow for a direct comparison of different approaches, potentially addressing different needs and preferences of patients, and also for more systematic research focusing on how psychological interventions affect not only psychological but also biological markers of stress. Both of these questions are addressed in the present study. Methods: A randomised controlled trial will be carried out to test and compare the effectiveness of three eight-week eHealth programmes for the mental health support of cancer patients. All programmes will be delivered through the same application for mobile devices MOU MindCare. N = 440 of breast cancer survivors will be recruited at the end of their adjuvant treatment (chemotherapy, radiotherapy, or both) and randomly assigned to one of the three interventions - Mindfulness-Based Cognitive Therapy for Cancer (MBCT-Ca), Positive Psychology (PP), or Autogenic Training (AT) - or the treatment-as-usual (TAU) control group. Psychological and biological markers of stress and adaptive functioning will be assessed at baseline (T0), post-treatment (T1), three-month follow-up (T2), and nine-month follow-up (T3). Primary outcomes will include heart-rate variability and self-report measures of depression, anxiety, perceived stress, general quality of life, and positive mental health. Secondary outcomes will include the levels of serum cortisol and immunomarkers, sleep quality, fatigue, common health symptoms, and several transdiagnostic psychological variables that are expected to be specifically affected by the MBCT-Ca and PP interventions, including dispositional mindfulness, emotion regulation, self-compassion, perceived hope, and gratitude. The data will be analysed using the mixed model repeated measures (MMRM) approach. Discussion: This trial is unique in comparing three different eHealth interventions for cancer patients based on three well-established approaches to mental health support delivered on the same platform. The study will allow us to examine whether different types of interventions affect different indicators of mental health. In addition, it will provide valuable data regarding the effects of stress-reducing psychological interventions on the biomarkers of stress playing an essential role in cancer recovery processes and general health.

Prediction of Vagal Nerve Stimulation Efficacy in Drug-Resistant Epilepsy (PRECISE): Prospective Study for Pre-implantation Prediction/Study Design.

Background: Vagal nerve stimulation (VNS) can be indicated in patients with drug-resistant epilepsy, who are not eligible for resective epilepsy surgery. In VNS therapy, the responder rate (i.e., percentage of subjects experiencing ≥50% seizure reduction) is ~50%. At the moment, there is no widely-accepted possibility to predict VNS efficacy in a particular patient based on pre-implantation data, which can lead to unnecessary surgery and improper allocation of financial resources. The principal aim of PRediction of vagal nerve stimulation EfficaCy In drug-reSistant Epilepsy (PRECISE) study is to verify the predictability of VNS efficacy by analysis of pre-implantation routine electroencephalogram (EEG). Methods: PRECISE is designed as a prospective multicentric study in which patients indicated to VNS therapy will be recruited. Patients will be classified as predicted responders vs. predicted non-responders using pre-implantation EEG analyses. After the first and second year of the study, the real-life outcome (responder vs. non-responder) will be determined. The real-life outcome and predicted outcome will be compared in terms of accuracy, specificity, and sensitivity. In the meantime, the patients will be managed according to the best clinical practice to obtain the best therapeutic response. The primary endpoint will be the accuracy of the statistical model for prediction of response to VNS therapy in terms of responders and non-responders. The secondary endpoint will be the quantification of differences in EEG power spectra (Relative Mean Power, %) between real-life responders and real-life non-responders to VNS therapy in drug-resistant epilepsy and the sensitivity and specificity of the model. Discussion: PRECISE relies on the results of our previous work, through which we developed a statistical classifier for VNS response (responders vs. non-responders) based on differences in EEG power spectra dynamics (Pre-X-Stim). Trial Registration: www.ClinicalTrials.gov, identifier: NCT04935567.

Electrodermal Response to Mirror Exposure in Relation to Subjective Emotional Responses, Emotional Competences and Affectivity in Adolescent Girls With Restrictive Anorexia and Healthy Controls.

Objective: Body image disturbances and the attendant negative emotions are two of the major clinical symptoms of eating disorders. The objective of the present experimental study was to shed more light on the degree of association or dissociation between the physiological and emotional response to mirror exposure in patients with restrictive mental anorexia, and on the relationships between the physiological response and characteristics connected with emotional processing. Materials and Methods: Thirty adolescent girls with the restrictive type of anorexia and thirty matched healthy controls underwent bilateral measurement of skin conductance (SC) during rest, neutral stimulus exposure, and mirror exposure, and completed a set of measures focused on emotion regulation competencies, affectivity, and eating disorder pathology. Results: Compared to healthy controls, girls with restrictive anorexia rated mirror exposure as a subjectively more distressful experience. Differences in skin conductance response (SCR) were not significant; however, variance in SCR was substantially greater in the group of anorexia patients as compared to healthy controls. The overall skin conductance level (SCL) was lower in anorexia patients. Increase in SCR during mirror exposure, as opposed to exposure to neutral stimuli, was positively related to the tendency to experience negative emotions, interoceptive sensitivity, body dissatisfaction and suppression, but not to other symptoms of eating pathology or emotional awareness. A post hoc analysis suggested that physiological reactivity might be associated with interoceptive sensitivity to mirror exposure especially in anorectic patients. Conclusion: The study seems to demonstrate some degree of dissociation between psychophysiological reactivity and subjective response to body exposure in patients with restrictive anorexia. Factors affecting differences in psychophysiological responsiveness to body exposure in anorectic patients require further exploration.

A Novel Statistical Model for Predicting the Efficacy of Vagal Nerve Stimulation in Patients With Epilepsy (Pre-X-Stim) Is Applicable to Different EEG Systems.

Background: Identifying patients with intractable epilepsy who would benefit from therapeutic chronic vagal nerve stimulation (VNS) preoperatively remains a major clinical challenge. We have developed a statistical model for predicting VNS efficacy using only routine preimplantation electroencephalogram (EEG) recorded with the TruScan EEG device (Brazdil et al., 2019). It remains to be seen, however, if this model can be applied in different clinical settings. Objective: To validate our model using EEG data acquired with a different recording system. Methods: We identified a validation cohort of eight patients implanted with VNS, whose preimplantation EEG was recorded on the BrainScope device and who underwent the EEG recording according to the protocol. The classifier developed in our earlier work, named Pre-X-Stim, was then employed to classify these patients as predicted responders or non-responders based on the dynamics in EEG power spectra. Predicted and real-world outcomes were compared to establish the applicability of this classifier. In total, two validation experiments were performed using two different validation approaches (single classifier or classifier voting). Results: The classifier achieved 75% accuracy, 67% sensitivity, and 100% specificity. Only two patients, both real-life responders, were classified incorrectly in both validation experiments. Conclusion: We have validated the Pre-X-Stim model on EEGs from a different recording system, which indicates its application under different technical conditions. Our approach, based on preoperative EEG, is easily applied and financially undemanding and presents great potential for real-world clinical use.

EEG Reactivity Predicts Individual Efficacy of Vagal Nerve Stimulation in Intractable Epileptics.

Background: Chronic vagal nerve stimulation (VNS) is a well-established non-pharmacological treatment option for drug-resistant epilepsy. This study sought to develop a statistical model for prediction of VNS efficacy. We hypothesized that reactivity of the electroencephalogram (EEG) to external stimuli measured during routine preoperative evaluation differs between VNS responders and non-responders. Materials and Methods: Power spectral analyses were computed retrospectively on pre-operative EEG recordings from 60 epileptic patients with VNS. Thirty five responders and 25 non-responders were compared on the relative power values in four standard frequency bands and eight conditions of clinical assessment-eyes opening/closing, photic stimulation, and hyperventilation. Using logistic regression, groups of electrodes within anatomical areas identified as maximally discriminative by n leave-one-out iterations were used to classify patients. The reliability of the predictive model was verified with an independent data-set from 22 additional patients. Results: Power spectral analyses revealed significant differences in EEG reactivity between responders and non-responders; specifically, the dynamics of alpha and gamma activity strongly reflected VNS efficacy. Using individual EEG reactivity to develop and validate a predictive model, we discriminated between responders and non-responders with 86% accuracy, 83% sensitivity, and 90% specificity. Conclusion: We present a new statistical model with which EEG reactivity to external stimuli during routine presurgical evaluation can be seen as a promising avenue for the identification of patients with favorable VNS outcome. This novel method for the prediction of VNS efficacy might represent a breakthrough in the management of drug-resistant epilepsy, with wide-reaching medical and economic implications.

Oscillatory reactivity to effortful cognitive processing in the subthalamic nucleus and internal pallidum: a depth electrode EEG study.

This study investigates how complex motor-cognitive activities are processed in the subthalamic nucleus (STN) and internal globus pallidum (GPi), as adverse neuropsychiatric effects may accompany deep brain stimulation (DBS), mainly in Parkinson's disease (PD) and STN-DBS. Dystonia patients with GPi-DBS electrodes (n = 5) and PD subjects (n = 5) with STN-DBS electrodes performed two tasks: (1) copying letters; and (2) writing any letter other than that appearing on the monitor. The cognitive load of the second task was greater than that of the first. Intracranial local field potentials (LFPs) were analysed. A beta power decrease was the main correlate of the enhanced cognitive load during the second task in both structures, with a lateralization to the left side, mainly in the GPi. A gamma power increase linked with the increased cognitive activity was observed only in the STN. Differences were also observed in the theta and alpha bandpasses. Beta ERD reactivity seems to be essential during the processing of complex motor-cognitive tasks, increases with enhanced cognitive effort, and was observed in both the STN and GPi. Oscillatory reactivity to effortful cognitive processing in other frequency bands was less consistent, with differences between the studied nuclei. Lateralization of activity related to cognitive factors was observed mainly in the GPi.

What's the meaning of this? A behavioral and neurophysiological investigation into the principles behind the classification of visual emotional stimuli.

Two experiments were performed to investigate the principles by which emotional stimuli are classified on the dimensions of valence and arousal. In Experiment 1, a large sample of healthy participants rated emotional stimuli according to both broad dimensions. Hierarchical cluster analyses performed on these ratings revealed that stimuli were clustered according to their semantic content at the beginning of the agglomerative process. Example semantic themes include food, violence, nudes, death, and objects. Importantly, this pattern occurred in a parallel fashion for ratings on both dimensions. In Experiment 2, we investigated if the same semantic clusters were differentiated at the neurophysiological level. Intracerebral EEG was recorded from 18 patients with intractable epilepsy who viewed the same set of stimuli. Not only did electrocortical responses differentiate between these data-defined semantic clusters, they converged with the behavioral measurements to highlight the importance of categories associated with survival and reproduction. These findings provide strong evidence that the semantic content of affective material influences their classification along the broad dimensions of valence and arousal, and this principle of categorization exerts an effect on the evoked emotional response. Future studies should consider data-driven techniques rather than normative ratings to identify more specific, semantically related emotional images.

The Role of Anterior Nuclei of the Thalamus: A Subcortical Gate in Memory Processing: An Intracerebral Recording Study.

OBJECTIVE: To study the involvement of the anterior nuclei of the thalamus (ANT) as compared to the involvement of the hippocampus in the processes of encoding and recognition during visual and verbal memory tasks. METHODS: We studied intracerebral recordings in patients with pharmacoresistent epilepsy who underwent deep brain stimulation (DBS) of the ANT with depth electrodes implanted bilaterally in the ANT and compared the results with epilepsy surgery candidates with depth electrodes implanted bilaterally in the hippocampus. We recorded the event-related potentials (ERPs) elicited by the visual and verbal memory encoding and recognition tasks. RESULTS: P300-like potentials were recorded in the hippocampus by visual and verbal memory encoding and recognition tasks and in the ANT by the visual encoding and visual and verbal recognition tasks. No significant ERPs were recorded during the verbal encoding task in the ANT. In the visual and verbal recognition tasks, the P300-like potentials in the ANT preceded the P300-like potentials in the hippocampus. CONCLUSIONS: The ANT is a structure in the memory pathway that processes memory information before the hippocampus. We suggest that the ANT has a specific role in memory processes, especially memory recognition, and that memory disturbance should be considered in patients with ANT-DBS and in patients with ANT lesions. ANT is well positioned to serve as a subcortical gate for memory processing in cortical structures.

Complex motor-cognitive factors processed in the anterior nucleus of the thalamus: an intracerebral recording study.

Cognitive adverse effects were reported after the deep brain stimulation (DBS) of the anterior nucleus of the thalamus (AN) in epilepsy. As the AN may have an influence on widespread neocortical networks, we hypothesized that the AN, in addition to its participation in memory processing, may also participate in cognitive activities linked with the frontal neocortical structures. The aim of this study was to investigate whether the AN might participate in complex motor-cognitive activities. Three pharmacoresistant epilepsy patients implanted with AN-DBS electrodes performed two tasks involving the writing of single letters: (1) copying letters from a monitor; and (2) writing of any letter other than that appearing on the monitor. The cognitive load of the second task was increased. The task-related oscillatory changes and evoked potentials were assessed. Local event-related alpha and beta desynchronization were more expressed during the second task while the lower gamma synchronization decreased. The local field event-related potentials were elicited by the two tasks without any specific differences. The AN participates in cognitive networks processing complex motor-cognitive tasks. Attention should be paid to executive functions in subjects undergoing AN-DBS.

Preictal dynamics of EEG complexity in intracranially recorded epileptic seizure: a case report.

Recent findings suggest that neural complexity reflecting a number of independent processes in the brain may characterize typical changes during epileptic seizures and may enable to describe preictal dynamics. With respect to previously reported findings suggesting specific changes in neural complexity during preictal period, we have used measure of pointwise correlation dimension (PD2) as a sensitive indicator of nonstationary changes in complexity of the electroencephalogram (EEG) signal. Although this measure of complexity in epileptic patients was previously reported by Feucht et al (Applications of correlation dimension and pointwise dimension for non-linear topographical analysis of focal onset seizures. Med Biol Comput. 1999;37:208-217), it was not used to study changes in preictal dynamics. With this aim to study preictal changes of EEG complexity, we have examined signals from 11 multicontact depth (intracerebral) EEG electrodes located in 108 cortical and subcortical brain sites, and from 3 scalp EEG electrodes in a patient with intractable epilepsy, who underwent preoperative evaluation before epilepsy surgery. From those 108 EEG contacts, records related to 44 electrode contacts implanted into lesional structures and white matter were not included into the experimental analysis.The results show that in comparison to interictal period (at about 8-6 minutes before seizure onset), there was a statistically significant decrease in PD2 complexity in the preictal period at about 2 minutes before seizure onset in all 64 intracranial channels localized in various brain sites that were included into the analysis and in 3 scalp EEG channels as well. Presented results suggest that using PD2 in EEG analysis may have significant implications for research of preictal dynamics and prediction of epileptic seizures.

Mismatch negativity-like potential (MMN-like) in the subthalamic nuclei in Parkinson's disease patients.

An infrequent change to an otherwise repetitive sequence of stimuli leads to the generation of mismatch negativity (MMN), even in the absence of attention. This evoked negative response occurs in the scalp-recorded electroencephalogram (EEG) over the temporal and frontal cortices, 100-250 ms after onset of the deviant stimulus. The MMN is used to detect sensory information processing. The aim of our study was to investigate whether MMN can be recorded in the subthalamic nuclei (STN) as evidence of auditory information processing on an unconscious level within this structure. To our knowledge, MMN has never been recorded in the human STN. We recorded intracerebral EEG using a MMN paradigm in five patients with Parkinson's disease (PD) who were implanted with depth electrodes in the subthalamic nuclei (STN). We found far-field MMN when intracerebral contacts were connected to an extracranial reference electrode. In all five PD patients (and nine of ten intracerebral electrodes), we also found near-field MMN-like potentials when intracerebral contacts were referenced to one another, and in some electrodes, we observed phase reversals in these potentials. The mean time-to-peak latency of the intracerebral MMN-like potentials was 214 ± 38 ms (median 219 ms). We reveal MMN-like potentials in bilateral STN. This finding provides evidence that STN receives sensory (auditory) information from other structures. The question for further research is whether STN receives such signals through a previously described hyperdirect pathway between STN and frontal cortex (a known generator of the MMN potential) and if the STN contributes to sensorimotor integration.

Subthalamic nucleus involvement in executive functions with increased cognitive load: a subthalamic nucleus and anterior cingulate cortex depth recording study.

We studied the appearance of broadband oscillatory changes (ranging 2-45 Hz) induced by a cognitive task with two levels of complexity. The event-related de/synchronizations (ERD/S) in the subthalamic nucleus (STN) and in the anterior cingulate cortex (ACC) were evaluated in an executive function test. Four epilepsy surgery candidates with intracerebral electrodes implanted in the ACC and three Parkinson's disease patients with externalized deep brain stimulation electrodes implanted in the STN participated in the study. A Flanker test (FT) with visual stimuli (arrows) was performed. Subjects reacted to four types of stimuli presented on the monitor by pushing the right or left button: congruent arrows to the right or left side (simple task) and incongruent arrows to the right or left side (more difficult complex task). We explored the activation of STN and the activation of the ACC while processing the FT. Both conditions, i.e. congruent and incongruent, induced oscillatory changes in the ACC and also STN with significantly higher activation during incongruent trial. At variance with the ACC, in the STN not only the ERD beta but also the ERD alpha activity was significantly more activated by the incongruent condition. In line with our earlier studies, the STN appears to be involved in activities linked with increased cognitive load. The specificity and complexity of task-related activation of the STN might indicate the involvement of the STN in processes controlling human behaviour, e.g. in the selection and inhibition of competing alternatives.

Hippocampal negative event-related potential recorded in humans during a simple sensorimotor task occurs independently of motor execution.

A hippocampal-prominent event-related potential (ERP) with a peak latency at around 450 ms is consistently observed as a correlate of hippocampal activity during various cognitive tasks. Some intracranial EEG studies demonstrated that the amplitude of this hippocampal potential was greater in response to stimuli requiring an overt motor response, in comparison with stimuli for which no motor response is required. These findings could indicate that hippocampal-evoked activity is related to movement execution as well as stimulus evaluation and associated memory processes. The aim of the present study was to investigate the temporal relationship between the hippocampal negative potential latency and motor responses. We analyzed ERPs recorded with 22 depth electrodes implanted into the hippocampi of 11 epileptic patients. Subjects were instructed to press a button after the presentation of a tone. All investigated hippocampi generated a prominent negative ERP peaking at ~420 ms. In 16 from 22 cases, we found that the ERP latency did not correlate with the reaction time; in different subjects, this potential could either precede or follow the motor response. Our results indicate that the hippocampal negative ERP occurs independently of motor execution. We suggest that hippocampal-evoked activity, recorded in a simple sensorimotor task, is related to the evaluation of stimulus meaning within the context of situation.

On the time course of synchronization patterns of neuronal discharges in the human brain during cognitive tasks.

Using intracerebral EEG recordings in a large cohort of human subjects, we investigate the time course of neural cross-talk during a simple cognitive task. Our results show that human brain dynamics undergo a characteristic sequence of synchronization patterns across different frequency bands following a visual oddball stimulus. In particular, an initial global reorganization in the delta and theta bands (2-8 Hz) is followed by gamma (20-95 Hz) and then beta band (12-20 Hz) synchrony.

The executive functions in frontal and temporal lobes: a flanker task intracerebral recording study.

The occurrence of the local generators of P3-like potentials elicited by a noise-compatibility flanker test was used to study the processing of executive functions, particularly in the frontal and temporal cortices. The test performed with arrows comprised a simpler congruent and a more difficult incongruent task. The two tasks activated the attention and several particular executive functions, i.e., working memory, time perception, initiation, and motor control of executed task. The incongruent task increased demand on executive functions, and besides the functions common for both tasks, an inhibition of automatic responses, the reversal of incorrect response tendency, the internal ordering of the correct response, and the initiation of the target-induced correct response were involved. In seven epilepsy surgery candidates (four men and three women), ranging in age from 26 to 38 years, multicontact depth electrodes were implanted in 590 cortical sites. In the two tasks, the P3-like potential sources were displayed in the mesial temporal structures, the lateral temporal neocortex, the anterior and posterior cingulate, the orbitofrontal cortex, and dorsolateral prefrontal cortex. The P3-like potentials occurred more frequently with the incongruent than with congruent stimuli in all these areas. This more frequent occurrence of P3 sources elicited by the incongruent task appeared significant in temporal lateral neocortex and orbitofrontal cortex. The executive functions are processed in a widespread frontotemporal neurocognitive network. This study confirms the involvement of the temporal neocortex in the executive functions.

Neural correlates of affective picture processing--a depth ERP study.

Using functional neuroimaging techniques (PET and fMRI), various cortical, limbic, and paralimbic structures have been identified in the last decade as neural substrates of human emotion. In this study we used a novel approach (intracerebral recordings of event-related potentials) to add to our knowledge of specific brain regions involved in affective picture processing. Ten intractable epileptic patients undergoing pre-surgical depth electrode recording viewed pleasant, neutral, and unpleasant pictures and intracerebral event-related potentials (ERPs) were recorded. A total of 752 cortical and subcortical sites were investigated. Significant differences in ERPs to unpleasant as compared to neutral or pleasant pictures were frequently and consistently observed in recordings from various brain areas--the mesial temporal cortex (the amygdala, the hippocampus, the temporal pole), the lateral temporal cortex, the mesial prefrontal cortex (ACC and the medial frontal gyrus), and the lateral prefrontal cortex. Interestingly, the mean latencies of responses to emotional stimuli were somewhat shorter in the frontal lobe structures (with evidently earlier activation within lateral prefrontal areas when compared to mesial prefrontal cortex) and longer in the temporal lobe regions. These differences, however, were not significant. Additional clearly positive findings were observed in some rarely investigated regions--in the posterior parietal cortex, the precuneus, and the insula. An approximately equivalent number of positive findings was revealed in the left and right hemisphere structures. These results are in agreement with a multisystem model of human emotion, distributed far beyond the typical limbic system and substantially comprising lateral aspects of both frontal lobes as well.

Chaos in schizophrenia associations, reality or metaphor?

There is evidence that schizophrenic associations display "chaotic", random-like behavior and decreased predictability. The evidence suggests a hypothesis that the "chaotic" mental disorganization could be explained within the concept of nonlinear dynamics and complexity in the brain that may cause chaotic neural organization. Testing of the hypothesis in the present study was performed using nonlinear analysis of bilateral electrodermal activity (EDA) during resting state and an association test in 56 schizophrenic patients and 44 healthy participants. EDA is a suitable measure of brain and autonomic activity reflecting neurobiological changes in schizophrenia that may indicate changes in nonlinear neural dynamics related to associative process. The results show that quantitative indices of chaotic dynamics (the largest Lyapunov exponents) calculated from EDA signals recorded during rest and the association test are significantly higher in schizophrenia patients than in the control group and increase during the test in comparison to the resting state. The difference was confirmed by statistical methods and using surrogate data testing that rejected an explanation within the linear statistical framework. The results provide supportive evidence that pseudo-randomness of schizophrenic associations and less predictability could be linked to increased complexity of nonlinear neural dynamics, although certain limitations in data interpretation must be taken into account.

Neural complexity, dissociation and schizophrenia.

BACKGROUND: Recent findings confirm, following Bleuler's and Janet's tradition, the significant influence of stress-related events and dissociation in the pathogenesis of schizophrenia. Dissociative reaction is most often a consequence of traumatic experiences that lead to a loss of inhibitory control and may produce split fragments of the mind. Recent findings in studies on brain complexity and neural synchronization suggest the hypothesis that the specific functional fragmentation of neural subsystems could be linked to the dissociation and splitting in schizophrenia that may be reflected in dynamic neural complexity and assessed by measures reflecting these processes. MATERIAL/METHODS: In this context, the hypothesis tested in this study is that dynamic changes in electrodermal activity (EDA) as a measure of brain and autonomic activity could serve as an indicator of specific changes in neural complexity in schizophrenia patients. Therefore, bilateral EDA under rest conditions in 30 schizophrenic patients and 30 healthy subjects was measured. RESULTS: The results of nonlinear and statistical analysis of EDA records indicated increased neural complexity indexed by a point-wise correlation dimension (PD2) in schizophrenia patients compared with healthy controls. CONCLUSIONS: This result represents preliminary support for the hypothesis that increased neural complexity reflects the functional fragmentation of neural subsystems related to traumatic dissociation and splitting in schizophrenia.