Pre-implant Heart Activity Differs in Responders and Non-responders to Vagal Nerve Stimulation Therapy in Epileptic Patients.

Vagal Nerve Stimulation (VNS) is used to treat patients with pharmacoresistant epilepsy. However, generally accepted tools to predict VNS response do not exist. Here we examined two heart activity measures - mean RR and pNN50 and their complex behavior during activation in pre-implant measurements. The ECG recordings of 73 patients (38 responders, 36 non-responders) were examined in a 30-sec floating window before (120 sec), during (2x120 sec), and after (120 sec) the hyperventilation by nose and mouth. The VNS response differentiation by pNN50 was significant (min p=0.01) in the hyperventilation by a nose with a noticeable descendant trend in nominal values. The mean RR was significant (p=0.01) in the rest after the hyperventilation by mouth but after an approximately 40-sec delay.Clinical Relevance- Our study shows that pNN50 and mean RR can be used to distinguish between VNS responders and non-responders. However, details of dynamic behavior showed how this ability varies in tested measurement segments.

Response to Vagal Stimulation by Heart-rate Features in Drug-resistant Epileptic Patients.

Vagal Nerve Stimulation (VNS) is an option in the treatment of drug-resistant epilepsy. However, approximately a quarter of VNS subjects does not respond to the therapy. In this retrospective study, we introduce heart-rate features to distinguish VNS responders and non-responders. Standard pre-implantation measurements of 66 patients were segmented in relation to specific stimuli (open/close eyes, photic stimulation, hyperventilation, and rests between). Median interbeat intervals were found for each segment and normalized (NMRR). Five NMRRs were significant; the strongest feature achieved significance with p=0.013 and AUC=0.66. Low mutual correlation and independence on EEG signals mean that presented features could be considered as an addition for models predicting VNS response using EEG.

Exploiting Graphoelements and Convolutional Neural Networks with Long Short Term Memory for Classification of the Human Electroencephalogram.

The electroencephalogram (EEG) is a cornerstone of neurophysiological research and clinical neurology. Historically, the classification of EEG as showing normal physiological or abnormal pathological activity has been performed by expert visual review. The potential value of unbiased, automated EEG classification has long been recognized, and in recent years the application of machine learning methods has received significant attention. A variety of solutions using convolutional neural networks (CNN) for EEG classification have emerged with impressive results. However, interpretation of CNN results and their connection with underlying basic electrophysiology has been unclear. This paper proposes a CNN architecture, which enables interpretation of intracranial EEG (iEEG) transients driving classification of brain activity as normal, pathological or artifactual. The goal is accomplished using CNN with long short-term memory (LSTM). We show that the method allows the visualization of iEEG graphoelements with the highest contribution to the final classification result using a classification heatmap and thus enables review of the raw iEEG data and interpret the decision of the model by electrophysiology means.

Respiratory-induced hemodynamic changes measured by whole-body multichannel impedance plethysmography.

The cardiovascular system is described by parameters including blood flow, blood distribution, blood pressure, heart rate and pulse wave velocity. Dynamic changes and mutual interactions of these parameters are important for understanding the physiological mechanisms in the cardiovascular system. The main objective of this study is to introduce a new technique based on parallel continuous bioimpedance measurements on different parts of the body along with continuous blood pressure, ECG and heart sound measurement during deep and spontaneous breathing to describe interactions of cardiovascular parameters. Our analysis of 30 healthy young adults shows surprisingly strong deep-breathing linkage of blood distribution in the legs, arms, neck and thorax. We also show that pulse wave velocity is affected by deep breathing differently in the abdominal aorta and extremities. Spontaneous breathing does not induce significant changes in cardiovascular parameters.

Heart sounds analysis using probability assessment.

OBJECTIVE: This paper describes a method for automated discrimination of heart sounds recordings according to the Physionet Challenge 2016. The goal was to decide if the recording refers to normal or abnormal heart sounds or if it is not possible to decide (i.e. 'unsure' recordings). APPROACH: Heart sounds S1 and S2 are detected using amplitude envelopes in the band 15-90 Hz. The averaged shape of the S1/S2 pair is computed from amplitude envelopes in five different bands (15-90 Hz; 55-150 Hz; 100-250 Hz; 200-450 Hz; 400-800 Hz). A total of 53 features are extracted from the data. The largest group of features is extracted from the statistical properties of the averaged shapes; other features are extracted from the symmetry of averaged shapes, and the last group of features is independent of S1 and S2 detection. Generated features are processed using logical rules and probability assessment, a prototype of a new machine-learning method. MAIN RESULTS: The method was trained using 3155 records and tested on 1277 hidden records. It resulted in a training score of 0.903 (sensitivity 0.869, specificity 0.937) and a testing score of 0.841 (sensitivity 0.770, specificity 0.913). The revised method led to a test score of 0.853 in the follow-up phase of the challenge. SIGNIFICANCE: The presented solution achieved 7th place out of 48 competing entries in the Physionet Challenge 2016 (official phase). In addition, the PROBAfind software for probability assessment was introduced.

Taming of the monitors: reducing false alarms in intensive care units.

False alarms in intensive care units represent a serious threat to patients. We propose a method for detection of five live-threatening arrhythmias. It is designed to work with multimodal data containing electrocardiograph and arterial blood pressure or photoplethysmograph signals. The presented method is based on descriptive statistics and Fourier and Hilbert transforms. It was trained using 750 records. The method was validated during the follow-up phase of the CinC/Physionet Challenge 2015 on a hidden dataset with 500 records, achieving a sensitivity of 93% (95%) and a specificity of 87% (88%) for real-time (retrospective) files. The given sensitivity and specificity resulted in score of 81.62 (84.96) for real-time (retrospective) records. The presented method is an improved version of the original algorithm awarded the first and the second prize in CinC/Physionet Challenge 2015.

SignalPlant: an open signal processing software platform.

The growing technical standard of acquisition systems allows the acquisition of large records, often reaching gigabytes or more in size as is the case with whole-day electroencephalograph (EEG) recordings, for example. Although current 64-bit software for signal processing is able to process (e.g. filter, analyze, etc) such data, visual inspection and labeling will probably suffer from rather long latency during the rendering of large portions of recorded signals. For this reason, we have developed SignalPlant-a stand-alone application for signal inspection, labeling and processing. The main motivation was to supply investigators with a tool allowing fast and interactive work with large multichannel records produced by EEG, electrocardiograph and similar devices. The rendering latency was compared with EEGLAB and proves significantly faster when displaying an image from a large number of samples (e.g. 163-times faster for 75 × 10(6) samples). The presented SignalPlant software is available free and does not depend on any other computation software. Furthermore, it can be extended with plugins by third parties ensuring its adaptability to future research tasks and new data formats.

Can we hear ventricle dyssynchrony? Yes, we can.

This study introduces a method for detection of ventricular depolarization activity and the transfer of this activity into an audible stereo audio signal. Heart potentials are measured by an ultra-high-frequency high-dynamic-range electrocardiograph (UHF-ECG) with a 25-kHz sampling rate. Averaged and prolonged UHF amplitude envelopes of V1-3 and V4-6 leads at a frequency range of 500-1000 Hz are used as a modulating function for two carrier audio frequencies. The right speaker makes it possible to listen to the depolarization of the septum and right ventricle (V1-3) and the left speaker the left ventricle lateral wall (V4-6). In the healthy heart, both speakers can be heard simultaneously. A delayed L or R speaker represents the dyssynchronous electrical activation of the ventricles. Examples of the normal heart, right bundle branch block and left bundle branch block can be heard at www.medisig.com/uhfecg.

Statistical significance of task related deep brain EEG dynamic changes in the time-frequency domain.

We present an off-line analysis procedure for exploring brain activity recorded from intra-cerebral electroencephalographic data (SEEG). The objective is to determine the statistical differences between different types of stimulations in the time-frequency domain. The procedure is based on computing relative signal power change and subsequent statistical analysis. An example of characteristic statistically significant event-related de/synchronization (ERD/ERS) detected across different frequency bands following different oddball stimuli is presented. The method is used for off-line functional classification of different brain areas.

The posterior medial cortex is involved in visual but not in verbal memory encoding processing: an intracerebral recording study.

The objective is to study the involvement of the posterior medial cortex (PMC) in encoding and retrieval by visual and auditory memory processing. Intracerebral recordings were studied in two epilepsy-surgery candidates with depth electrodes implanted in the retrosplenial cingulate, precuneus, cuneus, lingual gyrus and hippocampus. We recorded the event-related potentials (ERP) evoked by visual and auditory memory encoding-retrieval tasks. In the hippocampus, ERP were elicited in the encoding and retrieval phases in the two modalities. In the PMC, ERP were recorded in both the encoding and the retrieval visual tasks; in the auditory modality, they were recorded in the retrieval task, but not in the encoding task. In conclusion, the PMC is modality dependent in memory processing. ERP is elicited by memory retrieval, but it is not elicited by auditory encoding memory processing in the PMC. The PMC appears to be involved not only in higher-order top-down cognitive activities but also in more basic, rather than bottom-up activities.

Oscillatory changes in cognitive networks activated during a three-stimulus visual paradigm: an intracerebral study.

OBJECTIVE: The aim of this work was to study the oscillatory changes during target and distractor stimuli processing. We focused mainly on responses after distractor stimuli in the prefrontal cortex and their possible relation to our previous results from the basal ganglia. METHODS: Five epilepsy surgery candidates with implanted depth electrodes performed a three-stimulus paradigm. The frequent stimulus (70%; without required response) was a small blue circle, the target stimulus (15%; with motor response) was a larger blue circle, and the distractor stimulus (15%; without required response) was a checkerboard. The SEEG signals from 404 electrode contacts were analysed using event-related de/synchronization (ERD/S) methodology. RESULTS: The main response to the target stimuli was ERD in the alpha and low beta bands, predominantly in the motor control areas, parietal cortex and hippocampus. The distractor stimuli were generally accompanied by an early theta frequency band power increase most markedly in the prefrontal cortex. CONCLUSIONS: Different ERD/S patterns underline attentional shifting to rare target ("go") and distractor ("no-go") stimuli. SIGNIFICANCE: As an increase in lower frequency band power is considered to be a correlate of active inhibition, the prefrontal structures seem to be essential for inhibition of non-required movements.

Respiratory induced heart rate and blood pressure variability during mechanical ventilation in critically ill and brain death patients.

UNLABELLED: We analysed respiratory induced heart rate and blood pressure variability in mechanically ventilated patients with different levels of sedation and central nervous system activity. Our aim was to determine whether it is possible to distinguish different levels of sedation or human brain activity from heart rate and blood pressure. We measured 19 critically ill and 15 brain death patients ventilated at various respiratory frequencies - 15, 12, 8 and 6 breaths per minute. Basal and deeper sedation was performed in the critically ill patients. We detected and analysed heart rate and blood pressure parameters induced by ventilation. RESULTS: Respiratory induced heart rate variability is the unique parameter that can differentiate between brain death patients and sedated critically ill patients. Significant differences exist, especially during slow deep breathing with a mean period of 10 seconds. The limit values reflecting brain death are: baroreflex lower than 0.5 ms/mmHg and tidal volume normalised heart rate variability lower than 0.5 ms/ml. Reduced heart rate variability parameters of brain death patients remain unchanged even after normalisation to respiration volume. However, differences between basal and deep sedation do not appear significant on any parameter.

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.

Involvement of the subthalamic nucleus and globus pallidus internus in attention.

We studied the appearance of cognitive event-related potentials (ERPs) and event-related de/synchronizations (ERD/S) in the subthalamic nucleus (STN) and globus pallidus internus (GPi). We particularly focused on the rare non-target (distractor) stimuli processing. ERPs and ERD/S in the alpha and beta frequency range were analyzed in seven Parkinson's disease patients and one primary dystonia patient with implanted deep brain stimulation (DBS) electrodes. A visual three-stimulus protocol was used (frequent stimulus, target stimulus, and distractor). The non-target and distractor-related waveforms manifested similar shapes. A specific positive ERP peak around 200 ms and a low alpha frequency ERS were detected from the STN as a response to the distractor stimuli in six of the patients with Parkinson's disease and also in the primary dystonia patient's GPi. This positivity probably reflects an attentional orienting response to the distractor stimuli. The STN and GPi are probably involved in attentional cerebral networks.

Excitation specificity of repolarization parameters.

UNLABELLED: The excitation specificity of QT dynamic parameters was tested on three groups of subjects: healthy subjects; non-medicated hypertensive subjects with metabolic syndrome; and subjects with essential hypertension. Four different excitations of RR were used: bicycling exercise; tilt with breathing 0.1 and 0.33 Hz; and deep breathing. Linear dynamic feedback model of QT/RR coupling was supposed at the analysis and next repolarization parameters were tested: QTc; gain of QT/RR coupling for slow and fast RR variability; time constant of QT adaptation; and random QT variability. RESULTS: Dynamic repolarization parameters statistically significantly depend on the type of RR excitation. The gain of QT/RR coupling for slow RR variability, the time constant of QT adaptation and QTc are maximal at RR excitation given by the bicycling exercise. The frequency of breathing, i.e. corresponding vagal modulation has no effect on repolarization parameters. The measurements with deep breathing, without any other slow excitation of heart rate, has low signal-to-noise ratio of analyzed data and resulting QT parameters are inaccurate. CONCLUSION: The use of heart rate excitation and all measurements conditions should be defined for the exact analysis of the repolarization dynamic parameters.

Dynamic QT/RR coupling in patients with pacemakers.

The dynamic coupling between heart rate intervals (RR) and ventricular repolarization (QT) is analyzed. The analysis is based on measurements of 11 patients with pacemaker. In each measurement, there are at least 4 abrupt changes of RR preset by the pacemaker. With such a protocol, RR changes are important and well defined while disturbing factors and noise sources (such as those related with motion of patient) are minimized. The QT/RR coupling was described by 3 parameters (a1, b2, b3) transfer function (TRF) selected on the basis of a statistical analysis of performances of different TRF models. We found that our model is by far the best in its class: with more parameters (higher order models) the residuals remain almost the same while the extra parameters display variability much larger than that of our parameters. For all measurements, our TRF model describes more than 70% of QT variability. Within the patient set, we found interesting differences concerning dynamic non-linearity (response times longer with decreasing RR intervals than with increasing RR).

Blood pressure dynamics in hypertensive subjects during tilt table test.

Blood pressure dynamicity during tilt table measurement is discussed. We analyzed ECG and BP parameters from 14 normotensive young healthy volunteers, 15 old healthy volunteers, and two groups of hypertensive patients--20 non-medicated hypertensive subjects with no other known complications and 21 hypertensive non-medicated subjects with confirmed obesity (according to waist circumference), hyperlipidemia or diabetes mellitus. The dynamic parameters, such as pulse pressure, maximum of derivative BP, difference between maximum and minimum of derivative BP and SBP peak--DBP depression time were obtained from derivative continuous blood pressure signal recordings. We have found that the age factor plays a more significant role in dynamic parameters change and in inter-group differentiation than additional risk factors of hypertensive subjects.

Executive functions processed in the frontal and lateral temporal cortices: intracerebral study.

OBJECTIVE: The study was designed to investigate the neurocognitive network in the frontal and lateral temporal cortices that is activated by the complex cognitive visuomotor tasks of letter writing. METHODS: Eight epilepsy surgery candidates with implanted intracerebral depth electrodes performed two tasks involving the writing of single letters. The first task consisted of copying letters. In the second task, the patients were requested to write any other letter. The cognitive load of the second task was increased mainly by larger involvement of the executive functions. The task-related ERD/ERS of the alpha, beta and gamma rhythms was studied. RESULTS: The alpha and beta ERD as the activational correlate of writing of single letters was found in the sensorimotor cortex, anterior cingulate, premotor, parietal cortices, SMA and the temporal pole. The alpha and beta ERD linked to the increased cognitive load was present moreover in the dorsolateral and ventrolateral prefrontal cortex, orbitofrontal cortex and surprisingly also the temporal neocortex. Gamma ERS was detected mostly in the left motor cortex. CONCLUSIONS: Particularly the temporal neocortex was activated by the increased cognitive load. SIGNIFICANCE: The lateral temporal cortex together with frontal areas forms a cognitive network processing executive functions.

Noninvasive detection of vessel stiffness from continuous blood pressure recordings in hypertensive subjects.

This paper presents results of blood pressure dynamicity analysis aimed at vessel stiffness detection and subsequent cardiac risk stratification. We analyzed ECG and BP parameters from 12 normotensive young healthy volunteers, 10 old healthy volunteers, and two groups of hypertensive patients -- 12 young non-medicated hypertensive subjects with no other known complications and 16 hypertensive non-medicated subjects with confirmed obesity (according to waist circumference), hyperlipidemia or diabetes mellitus. The dynamic parameters obtained from a derivative continuous blood pressure signal provide additional information about vessel compliance. They can differentiate hypertensive subjects according to the level of cardiovascular risk.

Identical event-related potentials to target and frequent stimuli of visual oddball task recorded by intracerebral electrodes.

OBJECTIVE: The shape of visually elicited event-related potentials (ERP) of epileptic patients during their presurgical evaluation with intracerebral electrodes was investigated in the study. METHODS: Twenty intractable epileptic patients with depth electrodes at several intracranial locations in the frontal, temporal, parietal lobes, and in the amygdalo-hippocampal complex participated in the study. To evoke the ERP, a standard visual oddball task was used with target stimuli, and frequent non-habituated and habituated stimuli. The averaged responses of the 3 groups were superimposed and visually analyzed whether the shape appeared identical or non-identical. RESULTS: The EEG response to target and frequent stimuli was recorded in 660 intra-cerebral sites. In 88 sites (14 different patients) localized in the amygdala, parahippocampal gyrus, superior, middle, and inferior temporal gyri, fusiform and lingual gyri, sensorimotor cortex, prefrontal cortex, hippocampus, and cingulated gyrus, the identical ERPs to target and both groups of frequent stimuli were observed. In 442 sites located in the above listed structures, and in the basal ganglia and parietal cortex, the shape of the ERP differed from 0.3 to 0.47 s on after the stimulus. The remaining 130 sites did not yield the task-specific potential change. CONCLUSIONS: The existence of identical ERPs to target and frequent stimuli in the oddball task suggests that a part of mental operations underlying the brain engagement in this task is not dependent on the way of responding.