Time-Multiplexed Illumination for simultaneous Structural and Functional Voltage Sensitive Dye Recordings with a single Photo Sensor.

The in-vivo optical imaging of the cortical surface provides the ability to record different types of biophysiological signals, e.g., structural information, intrinsic signals, like blood oxygenation coupled reflection changes as well as extrinsic properties of voltage sensitive probes, like fluorescent voltage-sensitive dyes. The recorded data sets have very high temporal and spatial resolutions on a meso- to macroscopic scale, which surpass conventional multi-electrode recordings. Both, intrinsic and functional data sets, each provide unique information about temporal and spatial dynamics of cortical functioning, yet have individual drawbacks. To optimize the informational value it would thus be opportune to combine different types of optical imaging in a near simultaneous recording.Due to the low signal-to-noise ratio of voltage-sensitive dyes it is necessary to reduce stray light pollution below the level of the camera's dark noise. It is thus impossible to record full-spectrum optical data sets. We address this problem by a time-multiplexed illumination, bespoke to the utilized voltage sensitive dye, to record an alternating series of intrinsic and extrinsic frames by a high-frequency CMOS sensor. These near simultaneous data series can be used to compare the mutual influence of intrinsic and extrinsic dynamics (with regards to extracorporeal functional imaging) as well as for motion compensation and thus for minimizing frame averaging, which in turn results in increased spatial precision of functional data and in a reduction of necessary experimental data sets (3R principle).

Implementation and Long-Term Evaluation of a Hearing Aid Supported Tinnitus Treatment Using Notched Environmental Sounds.

Recent work has shown that sharp spectral edges in acoustic stimuli might have advantageous effects in the treatment of tonal tinnitus. In the course of this paper, we evaluate the long-term effects of spectrally notched hearing aids on the subjective tinnitus distress. By merging recent experimental work with a computational tinnitus model, we modified the commercially available behind-the-ear hearing aids so that a frequency band of 0.5 octaves, centered on the patient's individual tinnitus frequency, was blocked out. Those hearing aids employ a steep notch filter that filters environmental sounds to suppress the tinnitus-related changes in neural firing by lateral inhibition. The computational model reveals a renormalization of pathologically increased neural response reliability and synchrony in response to spectrally modified input. The target group, fitted with spectrally notched hearing aids, was matched with a comparable control group, fitted with standard hearing aids of the same type but without a notch filter. We analyze the subjective self-assessment by tinnitus questionnaires, and we monitor the objective distress correlates in auditory evoked response phase data. Both, subjective and objective results show a noticeable trend of a larger therapeutic benefit for notched hearing correction.

Lagrangian Motion Magnification revisited: Continuous, Magnitude Driven Motion Scaling for Psychophysiological Experiments.

Video motion magnification forms a relatively novel family of visualization techniques, that aim to magnify imperceivably small motions in videos. The most prominent techniques are based on Eulerian video processing and local phase shifting, which modify pixel time courses, rather than relying on explicit motion estimation.In this work, we show that under ideal conditions in the context of psychophysiological experiments, a Lagrangian motion magnification approach based on dense optical flow estimation, can be superior to Eulerian motion magnification strategies. We present a novel, continuous and motion magnitude driven forward warping scheme of small motions, which implements motion compensation and magnification into a single motion estimation step. Our approach does not rely on temporal filtering and works in the presence of large motion. It does not require the explicit identification of fast moving objects and more generally no segmentation and or matting in the image domain is necessary. We apply our method to the visualization of blinking related modulations in micro-saccadic eye movements ((i.a.. iridodonesis), pupil dilation (hippus) and micro-expression analysis.

Pyramid approach for the reduction of parallax-related artefacts in optical recordings of moving translucent volumes.

Functional optical imaging (OI) of intrinsic signals (like blood oxygenation coupled reflection changes) and of extrinsic properties of voltage sensitive probes (like voltage-sensitive dyes (VSD)) forms a group of invasive neuroimaging techniques, that possess up to date the highest temporal and spatial resolution on a meso- to macroscopic scale. There are different sources that contribute to the OI signal of which many are noise. In our previous works, we have used dense optical flow for the reduction of movement artefacts. The translucent surface of the cortex allows contributions from multiple depths. Due to the depth offield (DOF) effect, we get an implicit relation of depth and 2D frequency components. In this work, we introduce registration on the levels of a Laplacian pyramid to remove movement artefacts which have different motion components in different spatial frequency bands. This aims to resolve artefacts that remain after normal registration and are caused e.g. by parallax motion, dead pixels or dust on the sensor and other high frequent, moving particles on the cortex surface without the compromise of using high smoothness weights.

Thalamic gamma band desynchronization in a computational model of the auditory pathway.

Recent studies have focused on modeling the response of the early auditory processing stages to sound stimuli. However, the influence of sound on the higher stages like the auditory thalamus are not well identified. To understand how different sound stimuli affect the response of neurons in these higher stages, it is necessary to model the auditory pathway from the auditory nerve (AN) through the different stages up to the cortex. In this article we present a model of one of the paths through which sound travels from the AN to the cortex. The model presented is a compound of several sub models of different stages of the auditory pathway which offers a detailed resolution due to the subsequent simulation of processing stages. We consider neurons from the AN, the dorsal cochlear nucleus (DCN), the thalamus (specific and non-specific thalamic cells and reticular nucleus) and cortical columns simulating attended and unattended conditions. We use pure tone stimuli with different frequencies as an input and analyze the power spectra of the thalamic and cortical neurons. The main difference in the power spectra can be seen in the specific thalamic cells (STC), where a clear loss of power in the gamma band of the neurons responsible for processing the sound input occurred.

Motion invariant contrast enhancement of optical imaging data in the gradient domain.

Functional optical imaging (OI) of intrinsic signals (like blood oxygenation coupled reflection changes) and of extrinsic properties of voltage sensitive probes (like voltage-sensitive dyes (VSD)) forms a group of neuroimaging techniques that possess up to date highest temporal and spatial resolution on a meso-to macroscopic scale. An inherent problem of OI is a very low signal to noise ratio (SNR), which restricts the recordings to be completely motionless and requires detailed knowledge of the properties of the different noise sources. In our experiments we performed a durectomy and did not use an imaging chamber to allow us future joint electroencephalography-optical imaging (EEG-OI) measures, which resulted in movement artifacts. With the goal of motion compensation in OI recordings and magnification of signal changes, we present a novel processing pipeline, which is based on optic flow guided denoising and gradient domain tone mapping for spatiotemporal contrast enhancement.

Compensation of pulsation artifacts during optical imaging with and without cranial chamber.

Functional Optical Imaging (OI) through the opened skull forms a group of Neuroimaging techniques characterized by a high temporal and spatial resolution on a meso-to macroscopic scale. State of the art OI experiments are generally difficult to execute, with a very timely surgical preparation preceding the experiment, that requires a skilled surgeon to mount a sealed imaging chamber onto the skull. The chamber reduces brain pulsation artifacts and swelling of the brain through movement restriction. In this work, we present preliminary results of a novel approach that does not rely on the usage of an imaging chamber with the goal to facilitate heavily the surgical animal preparation and to allow straightforward joint Electroencephalography - Optical Imaging recordings in the future. We carried out experiments to compare the movement restricting properties of the imaging chamber with the movement in a recording of an unconstrained and periodically irrigated brain. We used high-level image processing techniques to reduce brain pulsation artifacts and did a quantitative movement analysis of the recordings. Our results suggest that while recordings with imaging chamber show less sagittal movement, both with and without imaging chamber comprise the same lateral movements.

Dysfunctional long term habituation to exogeneous tinnitus-matched sounds in patients with high tinnitus distress.

During the last years, the demand of accurate diagnostic tools for individualized tinnitus treatment gradually increased. Today several different psychometric instruments for the estimation of the patients degree of decompensation with clinical relevance have emerged. All of these tools are questionnaires for a subjective self-assessment and have deficits in comparability due to severe differences in their factor structure in the anamnesis. Those questionnaires thus they are only of limited value in the design of an individualized therapeutic approach. Objective diagnostic tools for the categorization of the patients' distress level are lacking in clinical routine. Scientific approaches yet demonstrated the feasibility of individual distress assessment by objective markers in the EEG. In this article we present the preliminary results of our study of a use of habituation correlates as objective indicator for the decompensation degree in high-distress tinnitus patients.

Neurofunctional model of large-scale correlates of selective attention governed by stimulus-novelty.

Multiple studies demonstrate the influence of the limbic system on the processing of sensory events and attentional guidance. But the mechanisms involved therein are yet not entirely clear. The close connection of handling incoming sensory information and memory retrieval, like in the case of habituation towards insignificant stimuli, suggests a crucial impact of the hippocampus on the direction of attention. In this paper we thus present a neurofunctional forward model of a hippocampal comparator function based on the theory of theta-regulated attention. Subsequently we integrated this comparator model into a multiscale framework for the simulation of evoked responses. The results of our simulations were compared to experimental data on electroencephalographic (EEG) correlates of habituation towards familiar stimuli using time-scale analysis. In consequence we are able to present additional evidence for limbic influences on the direction of attention driven by stimulus novelty and a systems neuroscience framework for the statements given in the theta-regulated attention hypothesis.

Modeling limbic influences on habituation deficits in chronic tinnitus aurium.

About 93% of healthy subjects suffer from tinnituslike symptoms when deprived of auditory stimuli, e.g., in a sound-proof chamber. This suggests an underlying physiological mechanism causing auditory sensations during absence of an external sound source. Grossberg suggested a mechanism by which hallucinations arise from mechanisms of learning, attention and volition. According to this mechanism notch-like hearing deficits are sufficient for experiencing auditory hallucinations, while their chronification is attributed to reorganization processes. In tinnitus sufferers the auditory sensation is accompanied by the inability to habituate to this endogenous sound. This disability might originate from a coactivation of brain areas that are only indirectly involved in cognitive processing such as areas belonging to the limbic system. Moreover subjective loudness of the tinnitus sensation is likely to depend on the amount of selective attention assigned to the tinnitus stream. Here we propose a functional model of pure-tone tinnitus in which exogenous and endogenous input into processing modules is represented as streams. We model the selection of the tinnitus stream at the subthalamic level according to its weighting. Then we propose a mechanism for the inability to habituate to this stream due to limbic coactivation and amplification by mechanisms of attentional guidance, and by the influence corticofugal projections on lower auditory processing stages. The model is able to replicate the phase stability of auditory evoked potentials as seen in tinnitus sufferers and controls.

Assessment of aversive stimuli dependent attentional binding by the N170 VEP component.

For social species nonverbal communication by assessment of emotion expression is crucial for building up and maintaining social structures. In humans, body language not only includes gestures but also a variety of facial expressions. Negative associated facial expressions, e.g. disgust, fear, anger call for a higher attentional binding due their evolutionary background, denoting directly personal dangers for the receptive individual. In a number of psychiatric disorders such as schizophrenia or autism spectrum diseases, the assessment of emotions in faces is disturbed, leading to even more pronounced social cuts. In this article we present a new methodology for monitoring the attentional binding to emotion-tinged stimuli in a face recognition task. We were able to demonstrate a significant difference in habituation behavior to neutral and negative associated faces respectively. In future, this methodology might provide a fast and reliable scheme for the detection of psychiatric disorders comprising dysfunction of limbic structures.

Corticothalamic feedback dynamics for neural correlates of auditory selective attention.

Auditory evoked cortical potentials (AECPs) have been consolidated as a diagnostic tool in audiology. Further applications of this technique are in experimental neuropsychology, neuroscience, and psychiatry, e.g., for the attention deficit disorder, schizophrenia, or for studying the tinnitus decompensation. In particular, numerous psychophysiological studies have emphasized their dynamic characteristics in relation to exogenous and endogenous attention. However, the effect of corticothalamic feedback dynamics to neural correlates of focal and nonfocal attention and its large-scale effect reflected in AECPs is far from being understood. To address this issue, we model neural correlates of auditory selective attention reflected in AECPs by using corticothalamic feedback dynamics. In our framework, we make use of a well-known multiscale model of evoked potentials, for which we define for the first time a neurofunctional map of relevant corticothalamic loops to the hearing path. Such loops are in turn are coupled to our proposed probabilistic scheme of auditory selective attention. It is concluded that our model represents a promising approach to gain a deeper understanding of the neurodynamics of auditory attention and might be used as an efficient forward model to support hypotheses that are obtained in experimental paradigms involving AECPs.

An integrative multiscale modeling approach for the study of tinnitus decompensation neural correlates.

The study of tinnitus has become of great interest due to the increasing number and severity of cases reported worldwide. To cope with such situation, many experimental and theoretical studies have been dedicated to gain deeper insight into the neurophysiological mechanisms involved in the tinnitus decompensation. In this direction, some of the most influential tinnitus models have emphasized the link between selective attention and the tinnitus decompensation. However, it is still not clear what are the mechanisms involved in such relation and wether it is possible to provide a neuropsychological framework linking them with respect to large-scale neural correlates. In order to address such issues, we make use of evoked cortical potential neural correlates of auditory selective attention. We thus propose an integrative multiscale modeling approach for large-scale neural correlates of selective attention in the tinnitus decompensation. The results of our simulations are compared with experimental data so that hypothesis can be validated.

Modeling neural correlates of auditory attention in evoked potentials using corticothalamic feedback dynamics.

Auditory evoked cortical potentials (AECP) are well established as diagnostic tool in audiology and gain more and more impact in experimental neuropsychology, neuro-science, and psychiatry, e.g., for the attention deficit disorder, schizophrenia, or for studying the tinnitus decompensation. The modulation of AECP due to exogenous and endogenous attention plays a major role in many clinical applications and has experimentally been studied in neuropsychology. However the relation of corticothalamic feedback dynamics to focal and non-focal attention and its large-scale effect reflected in AECPs is far from being understood. In this paper, we model neural correlates of auditory attention reflected in AECPs using corticothalamic feedback dynamics. We present a mapping of a recently developed multiscale model of evoked potentials to the hearing path and discuss for the first time its neurofunctionality in terms of corticothalamic feedback loops related to focal and non-focal attention. Our model reinforced recent experimental results related to online attention monitoring using AECPs with application as objective tinnitus decompensation measure. It is concluded that our model presents a promising approach to gain a deeper understanding of the neurodynamics of auditory attention and might be use as an efficient forward model to reinforce hypotheses that are obtained from experimental paradigms involving AECPs.