Individual Classification of Single Trial EEG Traces to Discriminate Brain responses to Speech with Different Signal-to-Noise Ratios.

To gain knowledge of listening effort in adverse situations, it is important to know how the brain processes speech with different signal-to-noise ratios (SNR). To investigate this, we conducted a study with 33 hearing impaired individuals, whose electroencephalographic (EEG) signals were recorded while listening to sentences presented in high and low levels of background noise. To discriminate between these two conditions, features from the 64-channel EEG recordings were extracted using the power spectrum obtained by a Fast Fourier Transform. Features vectors were selected on an individual basis by using the statistical R2 approach. The selected features were then classified by a Support Vector Machine with a nonlinear kernel, and the classification results were validated using a leave-one-out strategy, and presented an average classification accuracy over all 33 subjects of 83% (SD=6.4%). The most discriminative features were selected in the high-beta (19-30 Hz) and gamma (30-45 Hz) bands. These results suggest that specific brain oscillations are involved in addressing background noise during speech stimuli, which may reflect differences in cognitive load between the conditions of low and high background noise.

The prognostic value of the frontal QRS-T angle is comparable to cardiovascular autonomic neuropathy regarding long-term mortality in people with diabetes. A population based study.

Cardiovascular autonomic neuropathy (CAN) is a well known prognostic marker in diabetes. A large angle between the QRS- and the T-wave vector (QRS-T angle) in the electrocardiogram (ECG) has recently been introduced as another marker of poor prognosis. AIM: To assess and compare the long-term predictive power of the frontal plane QRS-T angle with CAN in people with diabetes. METHODS: In 1992-93 people with diabetes in the municipality of Horsens, Denmark, were identified by the prescription method andan age and gender stratified sample of 240 individuals with diabetes were randomly selected. The presence of CAN was defined using the heart rate response to Valsalva manoeuvre. The QRS-T angle was read using the method described by Gandhi. In July 2015 vital statistics were obtained fromthe Danish Civil Registration System. RESULTS: 178 individuals accepted to participate in the study, of which 153 (86%) completed the Valsalva manoeuvre and had sinus rhythm. Total observation time was 21.5 (0.18) years, in which 99 (65%) individuals died. An elevated QRS-T angle and the presence of cardiovascular autonomic neuropathy were both found to be significant predictors of death. In Cox regression analyses, adjusting for the effect of gender, age, duration of diabetes, BMI, total-cholesterol, diabetes type, haemoglobin A1c, smoking status, hypertension and previous MI, an independent prognostic value was found for the QRS-T angle as well as the Valsalva ratio. CONCLUSION: A large QRS-T angle and the presence of cardiovascular autonomic neuropathy are both strong and independent long-term predictors of all-cause mortality in people with diabetes.

Real-time estimation of eye gaze by in-ear electrodes.

Cognitive control of a hearing aid is the topic for several ongoing studies. The relevance of these studies should be seen in the light of inadequate steering of current hearing aids. While most studies are concerned with auditory attention tracking from the electroencephalogram (EEG), a complimentary approach may be to use visual attention tracking to steer the devices. Visual attention may be characterized by gaze direction, which can be obtained by electrooculography (EOG). EOG may be recorded from electrodes placed in the ear canal, termed EarEOG. To test the comparison of conventional EOG and EarEOG recordings, we conducted two experiments with six subjects. In the first experiment, the subjects were instructed to follow a moving dot on the screen moving in large saccades. In the second experiment, there were five large targets, and within each target, the dot had minor movements. When comparing conventional EOG and EarEOG, correlations of 0.9 and 0.91 with standard deviations of 0.02 were obtained for the two experiments respectively. To assess the feasibility of using EarEOG in real-time, correlation between EarEOG and the timecourse of the dot position was performed. When both signals were filtered with the same real-time applicable filter, correlations of 0.83 and 0.85 with standard deviations of 0.09 and 0.05 were found respectively to the two experiments. In conclusion, this study provides motivational aspects of using EarEOG to estimate eye gaze, as well as it identifies important future challenges in real-time applications to steer external devices such as a hearing aid.

Cortical and spinal assessment - a comparative study using encephalography and the nociceptive withdrawal reflex.

BACKGROUND: Standardized objective methods to assess the analgesic effects of opioids, enable identification of underlying mechanisms of drug actions in the central nervous system. Opioids may exert their effect on both cortical and spinal levels. In this study actions of morphine at both levels were investigated, followed by analysis of a possible correlation between the cortical processing and spinal transmission. METHODS: The study was conducted after a double-blinded, two-way crossover design in thirty-nine healthy participants. Each participant received 30mg morphine or placebo as oral solution in randomized order. The electroencephalogram (EEG) was recorded during rest and during immersion of the hand into ice-water. Electrical stimulation of the sole of the foot was used to elicit the nociceptive withdrawal reflex and the reflex amplitude was recorded. RESULTS: Data from thirty subjects was included in the data analysis. There was no change in the activity in resting EEG (P>0.05) after morphine administration as compared to placebo. During cold pressor stimulation, morphine significantly lowered the relative activity in the delta (1-4Hz) band (P=0.03) and increased the activity in the alpha (8-12Hz) band (P=0.001) as compared to placebo. The reflex amplitudes significantly decreased after morphine administration (P=0.047) as compared to placebo. There was no correlation between individual EEG changes during cold pressor stimulation and the decrease in the reflex amplitude after morphine administration (P>0.05). CONCLUSIONS: Cold pressor EEG and the nociceptive reflex were more sensitive to morphine analgesia than resting EEG and can be used as standardized objective methods to assess opioid effects. However, no correlation between the analgesic effect of morphine on the spinal and cortical assessments could be demonstrated.

Ear-EEG allows extraction of neural responses in challenging listening scenarios - A future technology for hearing aids?

Advances in brain-computer interface research have recently empowered the development of wearable sensors to record mobile electroencephalography (EEG) as an unobtrusive and easy-to-use alternative to conventional scalp EEG. One such mobile solution is to record EEG from the ear canal, which has been validated for auditory steady state responses and discrete event related potentials (ERPs). However, it is still under discussion where to place recording and reference electrodes to capture best responses to auditory stimuli. Furthermore, the technology has not yet been tested and validated for ecologically relevant auditory stimuli such as speech. In this study, Ear-EEG and conventional scalp EEG were recorded simultaneously in a discrete-tone as well as a continuous-speech design. The discrete stimuli were applied in a dichotic oddball paradigm, while continuous stimuli were presented diotically as two simultaneous talkers. Cross-correlation of stimulus envelope and Ear-EEG was assessed as a measure of ongoing neural tracking. The extracted ERPs from Ear-EEG revealed typical auditory components yet depended critically on the reference electrode chosen. Reliable neural-tracking responses were extracted from the Ear-EEG for both paradigms, albeit weaker in amplitude than from scalp EEG. In conclusion, this study shows the feasibility of extracting relevant neural features from ear-canal-recorded "Ear-EEG", which might augment future hearing technology.

Machine learning on encephalographic activity may predict opioid analgesia.

BACKGROUND: Opioids are used for the treatment of pain. However, 30-50% of patients have insufficient effect to the opioid initially selected by the physician, and there is an urgent need for biomarkers to select responders to the most appropriate drug. Since opioids mediate their effect in the central nervous system, this study aimed to investigate if electroencephalography (EEG) during rest or pain before treatment could predict the analgesic response. METHODS: EEG from 62 channels was recorded in volunteers during rest and tonic pain (cold pressor test). Morphine (30 mg) or placebo was then administered, and the pain test repeated 60 min after. Washout period between drugs was 7 days. Based on pain ratings, subjects were stratified into responders and non-responders. Spectral analysis was performed on the EEG. Conventional statistics on group basis were used and, furthermore, the most discriminative EEG features were subjected to support vector machine classification to predict the response for the individual subjects. RESULTS: Conventional statistics on the frequency bands revealed no differences between responders and non-responders. On the individual basis, no differences between groups were found using resting EEG. However, EEG during cold pain was able to classify responders with an accuracy of 72% (p = 0.01) and the result was reproducible using baseline data from both study days. CONCLUSIONS: Machine learning based on EEG before treatment enabled separation between responders and non-responders. This study represents the first step towards the prediction of opioid analgesia based on EEG features prior to drug administration, and advocates for the use of machine learning in future studies.

Dynamic spectral indices of the electroencephalogram provide new insights into tonic pain.

OBJECTIVE: This study aimed to investigate reliability of electroencephalography (EEG) during rest and tonic pain. Furthermore, changes in EEG between the two states as well as dynamics and relation to pain ratings were investigated. METHODS: On two separate days EEG was recorded in 39 subjects during rest and tonic pain (cold pressor test: left hand held in 2°C water for 2 min.) while pain intensity was rated continuously. Dynamic spectral analysis was performed on the EEG. Between-day reliability of spectral indices was assessed and correlations to pain ratings were investigated. RESULTS: EEG reliability was high during both states. The relative spectral indices increased in delta (1-4 Hz; P=0.0002), beta3 (18-32 Hz; P<0.0001) and gamma (32-70 Hz; P<0.0001) bands during tonic pain, and decreased in theta (4-8 Hz; P<0.0001), alpha1 (8-10 Hz; P<0.0001), alpha2 (10-12 Hz; P<0.0001) bands. Theta, beta3 and gamma bands correlated significantly to the area-under-curve of pain ratings, but only theta was dynamic and correlated to the pain ratings (R=0.88, P<0.0001). CONCLUSIONS: EEG assessed during tonic pain is a valid experimental pain model both in terms of reliability between days and in connection between cortical activity and pain perception. SIGNIFICANCE: EEG during tonic pain is more pain-specific and should be used in future basic and pharmacological studies.

Reproducibility of psychophysics and electroencephalography during offset analgesia.

BACKGROUND: Offset analgesia (OA) is a pain-inhibiting mechanism, defined as a disproportionately large decrease in pain perception in response to a discrete decrease in noxious stimulus intensity. Hence, the aims were (1) to investigate whether psychophysics and electroencephalography (EEG) can be assessed simultaneously during OA and (2) to assess whether OA is reproducible within the same day as well as between different days. METHODS: Two separate studies investigated OA: Study I (13 healthy volunteers; seven men; 25.5 ± 0.65 years) aimed at determining the feasibility of recording psychophysics and EEG simultaneously during OA. Study II (18 healthy volunteers; 12 men; 34 ± 3.15 years) assessed reproducibility of OA in terms of psychophysics and EEG. Subjects were presented to a 30-s OA heat stimulus paradigm on the volar forearm and psychophysics, and EEG recordings were obtained throughout the procedure. Reproducibility was assessed within the same day and between different days, using intraclass correlation coefficients (ICCs). Additionally, the reproducible psychophysical parameters were correlated to relevant EEG frequency bands. RESULTS: Simultaneous recording of psychophysics and EEG affects the frequency distribution in terms of alpha suppression. Reproducibility was proven for the psychophysics and EEG frequency bands both within the same day (all ICCs > 0.62) and between different days (all ICCs > 0.66, except for the delta band). Correlations between psychophysics and EEG were found in the theta (4-8 Hz), alpha (8-12 Hz) and gamma (32-80 Hz) bands (all p < 0.01). CONCLUSION: OA is a robust and reproducible model for experimental pain research, making it suitable for future research.

Cerebral excitability is abnormal in patients with painful chronic pancreatitis.

BACKGROUND: We investigated whether patients with painful chronic pancreatitis (CP) present abnormalities in the cerebral response to experimental pain stimuli. METHODS: Contact heat-evoked potentials (CHEPS) were recorded in 15 patients with CP and in 15 healthy volunteers during repetitive stimulation of the upper abdominal region (pancreatic 'viscerotome') and the right forearm (heterologous area). Three sequences of painful stimuli were applied at each site. Subjective pain scores were assessed by a visual analogue scale. Habituation was calculated as the relative change in CHEPS amplitudes between the first and the third stimulation sequence. RESULTS: As expected pain scores decreased in healthy volunteers during successive stimulations at both sites (i.e., habituation), while in the CP group, they remained unchanged. The cerebral response consisted of an early-latency, low-amplitude response (N1, contralateral temporal region) followed by a late, high-amplitude, negative-positive complex (N2/P2, vertex). During successive stimulation of the pancreatic area, N2/P2 amplitude increased 25% in CP patients, while they decreased 20% in healthy volunteers (p = 0.006). After stimulation of the forearm, N2/P2 amplitudes increased 3% in CP patients compared to a decrease of 20% in healthy volunteers (p = 0.06). CONCLUSIONS: Taken together, CP patients had an abnormal cerebral response to repetitive thermal stimuli. This was most prominent after stimulation of the upper abdominal area. As this area share spinal innervation with the pancreatic gland, these findings likely mirror distinctive abnormalities in cerebral pain processing.

Peripheral and central nervous contribution to gastrointestinal symptoms in diabetic patients with autonomic neuropathy.

BACKGROUND & AIMS: Long-term diabetes mellitus (DM) has been associated with neuronal changes in the enteric, peripheral and/or central nervous system. Moreover, abnormal visceral sensation and gastrointestinal (GI) symptoms are seen in up to 75% of patients. To explore the role of diabetic autonomic neuropathy (DAN) in patients with long-standing DM, we investigated psychophysical responses and neuronal activity recorded as evoked brain potentials and dipolar source modelling. METHODS: Fifteen healthy volunteers and 14 type-1 DM patients with DAN were assessed with a symptom score index characterizing upper GI abnormalities. Multichannel (62) electroencephalography was recorded during painful electrical stimulation of the lower oesophagus. Brain activity to painful stimulations was modelled using Brain Electrical Source Analysis (besa). RESULTS: Diabetic patients had higher stimulus intensities to evoke painful sensation (p ≤ 0.001), longer latencies of N2 and P2 components (both p ≤ 0.001), and lower amplitudes of P1-N2 and N2-P2 complexes (p ≤ 0.001; p = 0.02). Inverse modelling of brain sources showed deeper bilateral insular dipolar source localization (p = 0.002). Symptom score index was negatively correlated with the depth of insular activity (p = 0.004) and positively correlated with insular dipole strength (p = 0.03). CONCLUSION: DM patients show peripheral and central neuroplastic changes. Moreover, the role of abnormal insular processing may explain the appearance and persistence of GI symptoms related to DAN. This enhanced understanding of DAN may have future clinical and therapeutical implications.

Support vector regression correlates single-sweep evoked brain potentials to gastrointestinal symptoms in diabetes mellitus patients.

Diabetes mellitus (DM) is a multi-factorial and complex disease causing autonomic neuropathy and gastrointestinal symptoms in some patients. The neural mechanisms behind these symptoms are poorly understood, but it is believed that both peripheral and central mechanisms are involved. To gain further knowledge of the central mechanisms, the aim of this study was to identify biomarkers for the altered brain activity in type-1 DM patients compared to healthy volunteers (HV), and to correlate the obtained biomarkers to clinical patient scores. The study included 14 DM patients and 15 HV, with brain activity recorded as multi-channel electroencephalography evoked brain potentials (EPs) elicited by painful electrical stimulations in the esophagus. The single-sweep EPs were decomposed by an optimized discrete wavelet transform (DWT), and averaged for each channel. The DWT features from the DM patients were discriminated from the HV by a support vector machine (SVM) applied in regression mode. For the optimal DWT, the discriminative features were extracted and the SVM regression value representing the overall alteration of the EP was correlated to the clinical scores. A classification performance of 86.2% (P=0.01) was obtained by applying a majority voting scheme to the 5 best performing channels. The biomarker was identified as decreased theta band activity. The regression value was correlated to symptoms reported by the patients (P=0.04). The methodology is an improvement of the present approach to study central mechanisms in diabetes mellitus, and may provide a future application for a clinical tool to optimize treatment in individual patients.

Effects of isolated hyperinsulinaemia on sensory function in healthy adults.

AIMS: Gastrointestinal symptoms such as pain, bloating, nausea and vomiting are more frequent in pre-diabetic states as well as established diabetes, compared to healthy individuals. The mechanisms behind these symptoms are multi-factorial and complex. Furthermore, the effect of isolated hyperinsulinaemia on visceral and peripheral sensory function is poorly understood. Thus, the current study aimed to evaluate effects of acute hyperinsulinaemia on sensory function in healthy adults. METHODS: The sensitivity to electrical oesophageal and median nerve stimulation was assessed in 15 healthy volunteers together with recording of evoked brain potentials. All subjects were studied both fasting and using a euglycaemic hyperinsulinaemic clamp. RESULTS: There was on average a 15% increased sensitivity to oesophageal electrical stimulation during hyperinsulinaemia compared to fasting state (P<0.05), but the sensation after median nerve stimulation remained stable (P=0.58). No significant changes in latencies and amplitudes of evoked brain potentials were observed after oesophageal or median nerve stimulation (all P>0.05). CONCLUSIONS: This study suggests that acute isolated hyperinsulinaemia increases visceral sensitivity, but does not influence the somatic sensory function. The lack of changes in the evoked brain potentials may indicate that hyperinsulinaemia affects the visceral sensory system at a peripheral level. Our result suggests distinct functions of insulin in the various parts of the nervous system, and yields further clues to the significance of insulin as a satiety signal.

Randomised clinical trial: pregabalin attenuates experimental visceral pain through sub-cortical mechanisms in patients with painful chronic pancreatitis.

BACKGROUND: Pregabalin has a broad spectrum of analgesic and antihyperalgesic activity in both basic and clinical studies. However, its mechanisms and sites of action have yet to be determined in humans. AIMS: To assess the antinociceptive effect of pregabalin on experimental gut pain in patients with visceral hyperalgesia due to chronic pancreatitis and to reveal putative changes in corresponding central pain processing as assessed by evoked brain potentials. METHODS: Thirty-one patients were randomly assigned to receive increasing doses of pregabalin or placebo for three consecutive weeks. Perceptual thresholds to electrical stimulation of the sigmoid with recording of corresponding evoked brain potentials were obtained at baseline and study end. The brain source localisations reflecting direct neuronal activity were fitted by a five-dipole model projected to magnetic resonance imaging of the individuals' brains. RESULTS: As compared to placebo, pregabalin significantly increased the pain threshold to electrical gut stimulation from baseline (P=0.02). No differences in evoked brain potential characteristics were seen, neither after pregabalin nor placebo treatment (all P>0.05). In agreement with this, brain source locations remained stable during study treatment (all P>0.05). CONCLUSION: Pregabalin was superior to placebo for attenuation of experimental visceral pain in chronic pancreatitis patients. We suggest its antinociceptive effects to be mediated primarily through sub-cortical mechanisms.