Detection of information flow between cortical laminae activities and auditory evoked potentials in rats by means of Granger causality.

We seek to understand the relation between invasive high-resolution data and non-invasive measurement in an animal model in an auditory sensory adaptation experimental setting. In a previous study, we estimated the mutual information between the phase of auditory evoked responses (AER) with the phase of local field potentials (LFP) of auditory cortices at different frequency ranges. The results showed a consistently high level of information sharing between the AER activities as well as the responses from the granular layer, which was known as the main thalamo-recipient layer. However, mutual information was fundamentally an undirected measure of information flow. In this study we investigated how well we could characterize direction of information flow, by using Granger causality (GC), between different cortical laminae and functional projections on to the AER activities. We obtained that based on the GC coefficients, we are able to extract the connectivity between different cortical laminae to some extend and also a strong connection between the AER and granular layer. In our future study, we would like to construct a reliable picture of network connectivity, both functionally and anatomically, between different layers at more specified frequencies and much finer temporal resolutions.

Removal of spurious phase variations in oscillatory signals.

The study of oscillatory electroencephalogram (EEG) data has been one of the main sources for the analysis of different brain functions and decoding a variety of cognitive processes. One of the interesting features that has been the focus of study in the last decades is the study of instantaneous phase information in EEG. Phase synchronization techniques are among the main analysis tools that measure the degree of phase re-organization in signals. In phase re-organization approach, the phase alignment in stimulus induced potentials has been shown to be informative for decoding cognitive processes. Despite the developments in this area, the precision of measures may vary based on the level of noise. Phase distortion due to artefacts and a variety of pre-processing steps that are applied on data, can introduce artificial phase alignment. These artificial phase variations (that is referred to spurious phase variations) are not correlated to any stimulus or event. In a new study, it has been showed that a low instantaneous envelope lead to abrupt changes in IP, which could distort the results of phase synchronization. In this work, we propose a method that is able to estimate the true phase based on the measurements and estimate a standard deviation for the computed phase. The method enables to remove the effect of artificial phase changes due to low envelope. In this approach the analytic signal is modeled by a Kalman smoother, and estimates a more reliable version of the IP from the measurements. At last, we evaluate the model on different synthetic data sets.

Objective assessment of perceived effort in listening by employing EEG feature.

The adjustment of hearing aid devices can heavily depend on the subjective feedback of the patients. Our aim is to investigate measures that can be used objectively to state a subject's listening effort. To obtain a comprehensive and reliable measure as an indicator for a person's listening effort, we need to have a better understanding of electroencephalograpic (EEG) activities. Decoding EEG signals specifically by the analysis of the instantaneous phase information has been a new trend in the last decades. Throughout many studies conducted in the past, it has been shown that the instantaneous phase of oscillatory signals reset in relation to various cognitive processes. This is based on a hypothesis presented for the generation of event related potentials. In this study, we measure the degree of phase re-organization through fitting a von Mises distribution to EEG recordings. The concentration parameter of a von Mises distribution has been shown as an informative feature for reflecting the level of attention. This feature has been used for predicting the listening effort and the results are compared among three different hearing aid settings.

Motion reduction and multidimensional denoising in Voltage-sensitive Dye imaging.

Optical Imaging using Voltage-sensitive Dyes is characterized by low fractional changes in fluorescent light intensity upon the application of a stimulus, which leads to slight value differences between pixels on an in-general noisy image sequence. The application of an anisotropic diffusion filtering scheme, in order to contribute to the denoising of the optical images, is proposed as one option to improve its quality and for a better understanding of the physiological processes they represent. We apply an image registration approach to compensate for motion artifacts, such that we do not need to mount a fixed cranial chamber onto the skull. In this work, electrical stimulation to the tibial nerve in a rat model was used to register evoke potentials, imaging the somatosensory cortex of the animal, which was previously stained with the RH1691 dye.

Assessment of long-term habituation correlates in event-related potentials using a von Mises model.

In our preliminary work we were able to demonstrate habituation by analyzing attention correlates in single-trial sequences of auditory event-related potentials (ERPs). Despite different quantitative studies of instantaneous phase of ERPs in long-term habituation, there have been no former studies in generative process underlying the distribution of instantaneous phase information in the context of long-term habituation and its relation to attentional binding. For this means we used a von Mises model, representing the phase information over a set of single trial responses. Additionally we use a quantitative neurofunctional model to predict the dynamics of the instantaneous phase in single-trial ERP data during the long-term habituation. Measured habituation data is used to cross-validate the model's prediction. We conclude that the described method allows for an assessment of dynamic changes in the course of long-term habituation. The results also reinforce our neurofunctional multiscale model of long-term habituation and show the applicability of the described method for the experimental/clinical neurodiagnostic assessment of attentional binding.

Dysfunctional cortical inhibition in adult ADHD: neural correlates in auditory event-related potentials.

In recent times, the relevance of an accurate diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults has been the focus of several studies. No longer considered a pathology exclusive to children and adolescents, and taking into account its social implications, developing enhanced support tools for the current diagnostic procedure becomes a priority. Here we present a method for the objective assessment of ADHD in adults using chirp-evoked, paired auditory late responses (ALRs) combined with a two-dimensional ALR denoising scheme to extract correlates of intracortical inhibition. Our method allows for an effective single-sweep denoising, thus requiring less trials to obtain recognizable physiological features, useful as pointers of cortical impairment. Results allow an optimized diagnosis, reduction of data loss and acquisition time; moreover, they do not account exclusively for critical elements within clinical evaluations, but also allow studying the pathophysiology of the condition by providing objective information regarding impaired cortical functions.

Detection of change points in phase data: a Bayesian analysis of habituation processes.

Given a time series of data points, as obtained in biosignal monitoring, the change point problem poses the question of identifying times of sudden variations in the parameters of the underlying data distribution. We propose a method for extracting a discrete set of change points from directional data. Our method is based on a combination of the Bayesian change point model (CPM) and the Viterbi algorithm. We apply our method to the instantaneous phase information of single-trial auditory event-related potentials (ERPs) in a long term habituation paradigm. We have seen in previous studies that the phase information enters a phase-locked mode with respect to the repetition of a stimulus in the state of focused attention. With adaptation to an insignificant stimulus, attention tends to trail away (long-term habituation), characterized by changes in the phase signature, becoming more diffuse across trials. We demonstrate that the proposed method is suitable for detecting the effects of long-term habituation on phase information in our experimental setting.

Modeling prediction of a generalized habituation deficit in decompensated tinnitus sufferers.

The pathologic auditory sensation in decompensated tinnitus patients is accompanied by the inability to habituate even temporary to this sound. This disability might originate from simultaneous activation of brain areas for the appraisal of the stimulus valence as, e.g., the limbic system. This coactivation of limbic areas is likely to modulate the degree and persistence of selective attention assigned to the tinnitus stream, which in turn could also explain interindividual differences in tinnitus loudness perception. Preliminary studies demonstrate that the amount of allocated attention and the habituation deficit can be mapped to changes in auditory late evoked responses (ALRs). Utilizing a numerical model for the simulation of ALRs we were able to predict a general habituation behavior in two patient groups with different degrees of tinnitus severity. Evaluating the instantaneous phase of simulated and measured ALRs by its von Mises concentration parameter, we verify a habituation deficit relative to the degree of decompensation and thus provide additional support for our neurofunctional model of limbic influences on neural processing of sensory information.

On the objective assessment of the auditory brainstem response measurement quality.

Auditory Brainstem Responses (ABRs) are commonly used in clinical practice to determine hearing impairments and hearing thresholds. Although many research groups work on automatic recognition of ABRs - in order to decrease the acquisition times - measures to determine the quality of ABR measurements objectively are still missing. In fact, recently released new standards for electroencephalographic measurements in auditory examinations require an objective measurement quality assessment for neurodiagnostic devices. Thus there is a pressing need for the development and evaluation of such a quality control. In this study, we propose (a) a novel technique for the assessment of the ABR measurement quality and (b) evaluate and compare this technique to two other approaches which have been suggested in literature as required by the new standards.

Support of a patient-specific therapeutical acoustic stimulation in tinnitus by numerical modeling.

The pathogenesis of tinnitus involves multiple hierarchical levels of auditory processing and appraisal of sensory saliency. Early tinnitus onset is most likely attributed to homeostatic plasticity in the periphery, while the chronification and decompensation are tightly linked to brain areas for the allocation of attentional resources, such as e.g., the thalamocortical feedback loops and the limbic system. Increased spontaneous firing after sensory deafferentation might be sufficient to generate a phantom perception, yet the question why not every peripheral hearing loss automatically elicits a tinnitus sensation is still to be addressed. Utilizing quantitative modeling of multiple hierarchical levels in the auditory pathway, we demonstrate the effects of lateral inhibition on increased spontaneous firing and the resulting elevation of firing regularity and synchronization of neural activity. The presented therapeutical approach is based on the idea of disrupting the heightened regularity of the neural population response in the tinnitus frequency range. This neural activity regularity depends on lateral dispersion of common noise and thus is susceptible for edge effects and might be influenced by a change in neural activity in bordering frequency ranges by fitted acoustical stimulation. We propose the use of patient specifically adapted tailor-made notched acoustic stimulation, utilizing modeling results for the optimal adjustment of the stimulation frequencies to archive a therapeutical edge-effect.

Denoising of single-trial matrix representations using 2D nonlinear diffusion filtering.

In this paper we present a novel application of denoising by means of nonlinear diffusion filters (NDFs). NDFs have been successfully applied for image processing and computer vision areas, particularly in image denoising, smoothing, segmentation, and restoration. We apply two types of NDFs for the denoising of evoked responses in single-trials in a matrix form, the nonlinear isotropic and the anisotropic diffusion filters. We show that by means of NDFs we are able to denoise the evoked potentials resulting in a better extraction of physiologically relevant morphological features over the ongoing experiment. This technique offers the advantage of translation-invariance in comparison to other well-known methods, e.g., wavelet denoising based on maximally decimated filter banks, due to an adaptive diffusion feature. We compare the proposed technique with a wavelet denoising scheme that had been introduced before for evoked responses. It is concluded that NDFs represent a promising and useful approach in the denoising of event related potentials. Novel NDF applications of single-trials of auditory brain responses (ABRs) and the transcranial magnetic stimulation (TMS) evoked electroencephalographic responses denoising are presented in this paper.

Biocybernetics of attention in the tinnitus decompensation: An integrative multiscale modeling approach.

Tinnitus is one of the most common symptoms affecting people all over the world. In the absence of an established cure many individuals are not only faced with the need to adjust to the sensation of the tinnitus noise, but also with psychological comorbidities. In recent years, different studies have been directed to elucidate the psychophysiological mechanisms that are involved in the tinnitus decompensation. From these, special emphasis has been placed on studies related to attention and habituation, which accordingly play a crucial role in current tinnitus therapy approaches. In spite of such progress, the relationship between selective attention and the tinnitus decompensation with respect to large-scale neural correlates is still not well understood. In order to address this issue, we propose an integrative multiscale modeling approach for studying neural correlates of auditory selective attention in the tinnitus decompensation. Computational simulations based on our model confirmed electroencephalographic human data of both auditory selective attention and the tinnitus decompensation. It is concluded that the proposed methodology represents a promising approach to give insight into the neurodynamics of auditory selective attention in the tinnitus decompensation.

Causes of death in remote symptomatic epilepsy.

OBJECTIVE: To determine the causes of death of individuals with developmental disabilities that occur more frequently among those with remote symptomatic epilepsy (i.e., epilepsy occurring in persons with developmental delay or identified brain lesions) than for those without. METHODS: The authors compared causes of mortality in persons with (n = 10,030) and without (n = 96,163) history of epilepsy in a California population of persons with mild developmental disabilities, 1988 to 2002. Subjects had traumatic brain injury, cerebral palsy, Down syndrome, autism, or a developmental disability with other or unknown etiology. There were 721,759 person-years of data, with 2,397 deaths. Underlying causes of death were determined from the State of California's official mortality records. Cause-specific death rates and standardized mortality ratios (SMRs) were computed for those with and without epilepsy relative to subjects in the California general population. Comparisons were then made between SMRs of those with and without epilepsy, and CIs on the ratios of SMRs were determined. RESULTS: Death rates for persons with epilepsy were elevated for several causes. The greatest excess was due to seizures (International Classification of Diseases-9 [ICD-9] 345; SMR 53.1, 95% CI 28.0 to 101.0) and convulsions (ICD-9 780.3; SMR 25.2, 95% CI 11.7 to 54.2). Other causes occurring more frequently in those with epilepsy included brain cancer (SMR 5.2, 95% CI 2.2 to 12.1), respiratory diseases (SMR 1.7, 95% CI 1.2 to 2.5), circulatory diseases (SMR 1.3, 95% CI 1.0 to 1.7), and accidents (SMR 2.7, 95% CI 1.9 to 3.7), especially accidental drowning (SMR 12.8, 95% CI 7.0 to 23.2). CONCLUSIONS: Remote symptomatic epilepsy is associated with an increased risk of death. Seizures, aspiration pneumonia, and accidental drowning are among the leading contributors.

[Influence of interaural time- and level differences on the binaural interaction components in normal adults]. / Binaurale Differenzpotenziale: Normalwertebestimmung und Einfluss einer interauralen Zeit- und Pegeldifferenz.

BACKGROUND: Binaural interaction components of auditory brainstem responses have long been studied and its beta-wave has been shown to be correlated with directional hearing ability. As patients with auditory processing disorders such as patients with some sorts of learning disabilities frequently have difficulties with binaural processing it seems sensible to use binaural interaction components in the diagnosis of these disorders. METHODS: In order to obtain normal values and to investigate the influence of interaural time (ITD) and level differences (ILD) binaural interaction components were measured in 21 adults. Interaural time differences varied between 0 and 1.2 ms and interaural level differences between 0 and 30 dB. RESULTS: beta-latencies increased significantly as interaural time differences increased while beta-amplitudes did not change significantly. In measurements with higher interaural time differences detection of the beta-wave was only rarely possible. The effect of interaural level differences on beta-latencies was less pronounced and not significant as well as the influence of interaural level differences on beta-amplitudes. CONCLUSIONS: In the present study it could be shown that the beta-wave of the binaural interaction waveform is present in almost every normal hearing subject. As amplitudes show a considerable variation beta-latencies seem to be of higher diagnostic value than amplitudes.

Causes of death in autism.

The objective of this study was to determine which causes of death are more frequent in persons with autism, and by how much, compared with the general population. Subjects were 13,111 ambulatory Californians with autism, followed between 1983 and 1997. The units of study were person-years, each linked to the subject's age, sex, and cause of death (if any) for the specific year. Observed numbers of cause-specific deaths were compared with numbers expected according to general population mortality rates. Standardized mortality rates (SMRs) were computed for each mental retardation level. Elevated death rates were observed for several causes, including seizures and accidents such as suffocation and drowning; elevated mortality due to respiratory disease was observed among persons with severe mental retardation. Overall, excess mortality was especially marked for persons with severe mental retardation, but life expectancy is reduced even for persons who are fully ambulatory and who have only mild mental retardation.

Life expectancy of children in vegetative and minimally conscious states.

We determined estimates of survival in children, 3-15 years of age, in the vegetative state (VS) (n = 564), immobile minimally conscious state (MCS) (n = 705), and mobile MCS (n = 3,806). Data were extracted from the annual Client Development Evaluation Reports of the California Department of Developmental Services between 1988 and 1997 using the operational definitions for these three states on the basis of 15 descriptive behavioral categories. Patients were also categorized according to the following four etiologies: acquired (traumatic and nontraumatic) brain injury; perinatal/genetic; degenerative; and unknown/undetermined. The percentage of patients surviving 8 years was 63%, 65%, and 81%, for the VS, immobile MCS, and mobile MCS, respectively. Children in the VS and MCSs with acquired brain injury had lower mortality rates and those with degenerative diseases the highest mortality rates. We observed little difference in survival between patients in the VS and immobile MCS, suggesting that the presence of consciousness is not a critical variable in determining life expectancy. Furthermore, survival was much greater for patients in the mobile MCS than for those in the immobile MCS, suggesting that mobility is more important in predicting survival than the level of consciousness.

Life expectancy and median survival time in the permanent vegetative state.

The authors studied life expectancy and risk factors for mortality of persons in the vegetative state (VS). The study participants were 1,021 California patients in the VS during 1981-1996. Because of the large sample size, the authors were able to use multivariate methods to assess the effect of several risk factors on mortality. The authors found a strong secular trend in infant mortality, with rates in the mid-1990s being only one third of those in the early 1980s (P < 0.01). A smaller secular trend was observed for children aged 2-10 years and none for older patients. The mortality risk for older patients fell by approximately 8% for each year since the onset of the VS. The need for gastrostomy feeding was associated with a substantially higher risk, especially for infants and older patients (P < 0.01). Ventilator dependence also appeared to be a risk factor. On the basis of recent mortality rates, life expectancy in the VS is frequently higher than has generally been thought. For example, it is 10.5 additional years (+/- 2 years) for a 15-year-old patient who has been in the VS for 1 year, and 12.2 years for a 15-year-old patient who has been in the VS for 4 years.

Long-term survival of children and adolescents after traumatic brain injury.

OBJECTIVE: To obtain information on long-term mortality risk and life expectancy after traumatic brain injury (TBI), to improve planning and for counseling patients and their families. In contrast to the literature for spinal cord injury and other disabilities, there have been few such reports for TBI. DESIGN: Records were reviewed on 946 persons aged 5 to 21 years who had sustained TBI. All were patients who subsequently received disability services in California, 1987 to 1995. RESULTS: The chief predictors of mortality were basic functional skills such as mobility and self-feeding. After the initial high-risk period, mortality risk for TBI was much lower than for similarly functioning persons with cerebral palsy (a comparison group), although after 10 years the two sets of mortality rates had largely converged. For high-functioning persons, life expectancies were only 3 to 5 years shorter than for the general population. By contrast, the remaining life expectancy for those without mobility 6 months after injury was only 15 years.

Life expectancy of children with cerebral palsy.

Risk factors for mortality of young children with cerebral palsy were studied using a sample of 12,709 children aged 0.5-3.5 years with cerebral palsy who had received services from the State of California between 1980 and 1995. The most powerful prognostic factors for survival were simple functional items: mobility and feeding skills. Once these were known, factors such as severity of mental retardation and presence of quadriplegia contributed relatively little. Children with fair motor and eating skills had good survival prospects, with 90% or more reaching adulthood, but those without such skills had much poorer prospects. Among children who were unable to lift their heads, median survival time was 7 additional years for those who were tube fed (n = 557) and 14 years for those fed entirely by others (n = 997). Although a child's approximate survival chances can be assessed from such functional classifications, we indicate the manner in which additional information on the child's condition can be used to obtain more accurate survival data.