MRI signs helpful in the differentiation of patients with anterior ischaemic optic neuropathy and optic neuritis.

BACKGROUND/AIMS: The aim of this study was to identify specific MRI characteristics of anterior ischaemic optic neuropathy (AION) and optic neuritis (ON) that would aid in the differentiation between these two diagnoses. METHODS: We retrospectively analysed a consecutive case series including all patients with an MRI study of brain and orbit and the clinical diagnosis of either ON or AION. We examined the scans for restricted diffusion of the optic nerve, optic sheath diameter, enhancement and location of enhancement of the optic nerve and distribution of the white matter lesions. RESULTS: Fifty patients met the inclusion criteria. We found an accuracy of 0.98 for the discrimination between AION and ON based solely on parameters extracted from MRI data. Dominance analysis to determine the most influential parameters showed that the enhancement pattern of the optic nerve and distribution of the white matter lesions had the biggest impact on the classification and led to a discrimination accuracy of 0.9 when used alone. CONCLUSION: In patients with an inconclusive clinical diagnosis, optic nerve enhancement pattern and distribution of white matter lesions can aid in the diagnosis and differentiation between AION and ON. Diffusion-weighted imaging did not add significant information to the diagnosis or help to differentiate between the two conditions.

Retinal layer segmentation in a cohort of healthy children via optical coherence tomography.

BACKGROUND: High-resolution optical coherence tomography (OCT) allows the detection of macular pathology and involvement of the optic nerve in a wide spectrum of diseases. For the differentiation of diseased and healthy status, normal values of retinal layer segmentation are critical. Yet, normative values mostly cover adult populations with only sparse data for paediatric cohorts. We present data of retinal layer characteristics via OCT in a healthy paediatric cohort. METHODS: This prospective cross-sectional study screened 75 healthy children (male = 42, female = 33, range 4-17 years) without visual problems. OCT was performed with a peripapillary ring and macula scan protocol to determine paediatric normative values for routine parameters (peripapillary retinal nerve fibre layer thickness (pRNFL), total macular volume (TMV), macular retinal thickness (RT)). The macula scan (6mm grid) was segmented using the device-inherent automated segmentation software (Heidelberg Eye Explorer) for retinal layers: RNFL, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL) in 9 segments each and mean of the 9 segments. RESULTS: We obtained OCT data of 72 children with mean age 12.49 years (standard deviation, SD, 2.18; minimum 3.93). Mean global pRNFL was 102.20 µm (SD 8.24), mean TMV 8.81 mm3 (0.30) and mean RT (all segments) 318.22 µm (10.19). Segmented macular retinal layer thicknesses (mean of all segments) were: RNFL 27.67 µm (2.14), GCL 41.94 µm (2.50), IPL 34.97 µm (2.10), INL 35.18 µm (2.15), OPL 29.06 µm (2.24), ONL 68.35 µm (6.20). CONCLUSION: The OCT is a useful non-invasive imaging technique for the examination of the retina in children with short duration, high imaging resolution and no known adverse effects. Normative values may serve as a comparator for different neuropaediatric disorders and are first presented with this study using an up-to-date and standardized OCT imaging technique.

Pharmacological and Behavioral Strategies to Improve Vision in Acquired Pendular Nystagmus.

BACKGROUND Acquired pendular nystagmus (APN) is a back and forth, oscillatory eye movement in which the 2 oppositely directed slow phases have similar waveforms. APN occurs commonly in multiple sclerosis and causes a disabling oscillopsia that impairs vision. Previous studies have proven that symptomatic therapy with gabapentin or memantine can reduce the nystagmus amplitude or frequency. However, the effect of these medications on visual acuity (VA) is less known and to our knowledge the impact of non-pharmacological strategies such as blinking on VA has not been reported. This is a single observational study without controls (Class IV) and is meant to suggest a future strategy for study of vision in patients with disabling nystagmus and impaired vision. CASE REPORT A 49-year-old woman with primary progressive multiple sclerosis with spastic paraparesis and a history of optic atrophy presented with asymmetrical binocular APN and bothersome oscillopsia. We found that in the eye with greater APN her visual acuity improved by 1 line (from 0.063 to 0.08 decimals) immediately after blinking. During treatment with memantine, her VA without blinking increased by 2 lines, from 0.063 to 0.12, but improved even more (from 0.12 to 0.16) after blinking. In the contralateral eye with a barely visible nystagmus, VA was reduced by 1 line briefly (~500 ms) after blinking. CONCLUSIONS In a patient with APN, blinking transiently improved vision. The combination of pharmacological treatment with memantine and the blinking strategy may induce better VA and less oscillopsia than either alone.

Differences in morphology and visual function of myelin oligodendrocyte glycoprotein antibody and multiple sclerosis associated optic neuritis.

BACKGROUND: Myelin oligodendrocyte glycoprotein immunoglobulin G associated optic neuritis (MOG-ON) is a recently described entity. Recent studies have shown that MOG-ON has a more severe clinical presentation than classic optic neuritis (ON). OBJECTIVE: This study aimed to define morphological characteristics of MOG-ON, correlate these with clinical characteristics and compare them with multiple sclerosis associated ON (MS-ON) and healthy controls (CTRL). METHODS: In a retrospective study, we included MOG-ON and MS-ON patients seen between 2011 and 2018 at the University Hospital Bern. Data from clinical examination, perimetry, and optical coherence tomography (OCT) were analyzed. RESULTS: A total of 66 eyes of 43 patients were included; 22 MS-ON and 33 CTRL eyes were sex- and age-matched to 11 MOG-ON eyes. We found significantly worse visual acuity at nadir, but better recovery and thinner global peripapillary retinal nerve fiber layer thickness in MOG-ON patients compared to MS-ON patients. Both groups exhibited irregular thinning of the macular ganglion cell layer. Furthermore, the visual acuity and visual field parameters correlated to retinal layer thickness only in MOG-ON eyes. CONCLUSION: In comparison to MS-ON, MOG-ON is associated with more prominent acute vision loss and more pronounced global thinning of the pRNFL. Both entities result in similar final visual acuity and atrophy of the macular ganglion cell layer.

Homonymous hemiatrophy of ganglion cell layer from retrochiasmal lesions in the visual pathway.

OBJECTIVE: To determine the temporal evolution, morphology, and frequency of macular ganglion cell atrophy in patients with retrochiasmal lesions of the visual pathway. METHODS: In a consecutive retrospective case series, we identified 47 patients with homonymous hemianopia and accessible macular optical coherence tomography scans. We estimated the time of lesion onset and the location of the lesion within the afferent visual pathway. Using semiautomatic layer segmentation, we determined ganglion cell layer thickness in areas projecting to the side of the retrochiasmal lesion and compared it with ganglion cell layer thickness on the healthy side. RESULTS: We found that retrochiasmal lesions at any level may be associated with an atrophy of ganglion cells. This atrophy respects the vertical midline through the fovea and thus the anatomic separation of the nasal and temporal visual field. The vertical line separating the affected from the unaffected side has significantly less tilt as compared with the disc-fovea angle. Lesions of the optic tract are associated with earlier macular ganglion cell atrophy than retrogeniculate lesions. Macular ganglion cell atrophy may be present in cases with normal peripapillary nerve fiber layer analysis and vice versa. CONCLUSIONS: Macular ganglion cell layer thickness shows a topographic hemiatrophy in retrochiasmal lesions, which manifests earlier for tract lesions than for retrogeniculate lesions. This additional examination of ganglion cell homonymous hemiatrophy has a higher sensitivity in detecting retrograde transsynaptic degeneration than the analysis of the peripapillary nerve fiber layer alone.

Support for the slip hypothesis from whisker-related tactile perception of rats in a noisy environment.

Rodents use active whisker movements to explore their environment. The "slip hypothesis" of whisker-related tactile perception entails that short-lived kinematic events (abrupt whisker movements, called "slips", due to bioelastic whisker properties that occur during active touch of textures) carry the decisive texture information. Supporting this hypothesis, previous studies have shown that slip amplitude and frequency occur in a texture-dependent way. Further, experiments employing passive pulsatile whisker deflections revealed that perceptual performance based on pulse kinematics (i.e., signatures that resemble slips) is far superior to the one based on time-integrated variables like frequency and intensity. So far, pulsatile stimuli were employed in a noise free environment. However, the realistic scenario involves background noise (e.g., evoked by rubbing across the texture). Therefore, if slips are used for tactile perception, the tactile neuronal system would need to differentiate slip-evoked spikes from those evoked by noise. To test the animals under these more realistic conditions, we presented passive whisker-deflections to head-fixed trained rats, consisting of "slip-like" events (waveforms mimicking slips occurring with touch of real textures) embedded into background noise. Varying the (i) shapes (ramp or pulse); (ii) kinematics (amplitude, velocity, etc.); and (iii) the probabilities of occurrence of slip-like events, we observed that rats could readily detect slip-like events of different shapes against noisy background. Psychophysical curves revealed that the difference of slip event and noise amplitude determined perception, while increased probability of occurrence (frequency) had barely any effect. These results strongly support the notion that encoding of kinematics dominantly determines whisker-related tactile perception while the computation of frequency or intensity plays a minor role.

Spine loss in primary somatosensory cortex during trace eyeblink conditioning.

Classical conditioning that involves mnemonic processing, that is, a "trace" period between conditioned and unconditioned stimulus, requires awareness of the association to be formed and is considered a simple model paradigm for declarative learning. Barrel cortex, the whisker representation of primary somatosensory cortex, is required for the learning of a tactile variant of trace eyeblink conditioning (TTEBC) and undergoes distinct map plasticity during learning. To investigate the cellular mechanism underpinning TTEBC and concurrent map plasticity, we used two-photon imaging of dendritic spines in barrel cortex of awake mice while being conditioned. Monitoring layer 5 neurons' apical dendrites in layer 1, we show that one cellular expression of barrel cortex plasticity is a substantial spine count reduction of ∼15% of the dendritic spines present before learning. The number of eliminated spines and their time of elimination are tightly related to the learning success. Moreover, spine plasticity is highly specific for the principal barrel column receiving the main signals from the stimulated vibrissa. Spines located in other columns, even those directly adjacent to the principal column, are unaffected. Because layer 1 spines integrate signals from associative thalamocortical circuits, their column-specific elimination suggests that this spine plasticity may be the result of an association of top-down signals relevant for declarative learning and spatially precise ascending tactile signals.

Vibrotactile discrimination in the rat whisker system is based on neuronal coding of instantaneous kinematic cues.

Which physical parameter of vibrissa deflections is extracted by the rodent tactile system for discrimination? Particularly, it remains unclear whether perception has access to instantaneous kinematic parameters (i.e., the details of the trajectory) or relies on temporally integration of the movement trajectory such as frequency (e.g., spectral information) and intensity (e.g., mean speed). Here, we use a novel detection of change paradigm in head-fixed rats, which presents pulsatile vibrissa stimuli in seamless sequence for discrimination. This procedure ensures that processes of decision making can directly tap into sensory signals (no memory functions involved). We find that discrimination performance based on instantaneous kinematic cues far exceeds the ones provided by frequency and intensity. Neuronal modeling based on barrel cortex single units shows that small populations of sensitive neurons provide a transient signal that optimally fits the characteristic of the subject's perception. The present study is the first to show that perceptual read-out is superior in situations allowing the subject to base perception on detailed trajectory cues, that is, instantaneous kinematic variables. A possible impact of this finding on tactile systems of other species is suggested by evidence for instantaneous coding also in primates.

Are spatial frequency cues used for whisker-based active discrimination?

Rats are highly skilled in discriminating objects and textures by palpatory movements of their whiskers. If they used spatial frequency cues, they would be able to optimize performance in a stimulus dependent way-by moving their whisker faster or slower across the texture surface, thereby shifting the frequency content of the neuronal signal toward an optimal working range for perception. We tested this idea by measuring discrimination performance of head-fixed rats that were trained to actively sample from virtual grids. The virtual grid mimicked discrete and repetitive whisker deflections generated by real objects (e.g., grove patterns) with single electrical microstimulation pulses delivered directly to the barrel cortex, and provided the critical advantage that stimuli could be controlled at highest precision. Surprisingly, rats failed to use the spatial frequency cue for discrimination as a matter of course, and also failed to adapt whisking patterns in order to optimally exploit frequency differences. In striking contrast they could be easily trained to discriminate stimuli differing in electrical pulse amplitudes, a stimulus property that is not malleable by whisking. Intermingling these "easy-to-discriminate" discriminanda with others that solely offered frequency/positional cues, rats could be guided to base discrimination on frequency and/or position, albeit on a lower level of performance. Following this training, abolishment of electrical amplitude cues and reducing positional cues led to initial good performance which, however, was unstable and ran down to very low levels over the course of hundreds of trials. These results clearly demonstrate that frequency cues, while definitely perceived by rats, are of minor importance and they are not able to support consistent modulation of whisking patterns to optimize performance.

Estimation of diffusion coefficients from voltammetric signals by support vector and gaussian process regression.

BACKGROUND: Support vector regression (SVR) and Gaussian process regression (GPR) were used for the analysis of electroanalytical experimental data to estimate diffusion coefficients. RESULTS: For simulated cyclic voltammograms based on the EC, Eqr, and EqrC mechanisms these regression algorithms in combination with nonlinear kernel/covariance functions yielded diffusion coefficients with higher accuracy as compared to the standard approach of calculating diffusion coefficients relying on the Nicholson-Shain equation. The level of accuracy achieved by SVR and GPR is virtually independent of the rate constants governing the respective reaction steps. Further, the reduction of high-dimensional voltammetric signals by manual selection of typical voltammetric peak features decreased the performance of both regression algorithms compared to a reduction by downsampling or principal component analysis. After training on simulated data sets, diffusion coefficients were estimated by the regression algorithms for experimental data comprising voltammetric signals for three organometallic complexes. CONCLUSIONS: Estimated diffusion coefficients closely matched the values determined by the parameter fitting method, but reduced the required computational time considerably for one of the reaction mechanisms. The automated processing of voltammograms according to the regression algorithms yields better results than the conventional analysis of peak-related data.

Real-time adaptive microstimulation increases reliability of electrically evoked cortical potentials.

Cortical neuroprostheses that employ repeated electrical stimulation of cortical areas with fixed stimulus parameters, are faced with the problem of large trial-by-trial variability of evoked potentials. This variability is caused by the ongoing cortical signal processing, but it is an unwanted phenomenon if one aims at imprinting neural activity as precisely as possible. Here, we use local field potentials measured by one microelectrode, located at a distance of 200 microns from the stimulation site, to drive the electrically evoked potential toward a desired target potential by real-time adaptation of the stimulus intensity. The functional relationship between ongoing cortical activity, evoked potential, and stimulus intensity was estimated by standard machine learning techniques (support vector regression with problem-specific kernel function) from a set of stimulation trials with randomly varied stimulus intensities. The smallest deviation from the target potential was achieved for low stimulus intensities. Further, the observed precision effect proved time sensitive, since it was abolished by introducing a delay between data acquisition and stimulation. These results indicate that local field potentials contain sufficient information about ongoing local signal processing to stabilize electrically evoked potentials. We anticipate that adaptive low intensity microstimulation will play an important role in future cortical prosthetic devices that aim at restoring lost sensory functions.

Automatic cluster detection in Kohonen's SOM.

Kohonen's self-organizing map (SOM) is a popular neural network architecture for solving problems in the field of explorative data analysis, clustering, and data visualization. One of the major drawbacks of the SOM algorithm is the difficulty for nonexpert users to interpret the information contained in a trained SOM. In this paper, this problem is addressed by introducing an enhanced version of the Clusot algorithm. This algorithm consists of two main steps: 1) the computation of the Clusot surface utilizing the information contained in a trained SOM and 2) the automatic detection of clusters in this surface. In the Clusot surface, clusters present in the underlying SOM are indicated by the local maxima of the surface. For SOMs with 2-D topology, the Clusot surface can, therefore, be considered as a convenient visualization technique. Yet, the presented approach is not restricted to a certain type of 2-D SOM topology and it is also applicable for SOMs having an n-dimensional grid topology.