Consensus statement on prevention and management of adverse effects following rejuvenation procedures with hyaluronic acid-based fillers.

Facial fillers play an important role in the correction of facial changes associated with ageing. They offer quick treatments in the outpatient setting with minimal subsequent downtime that provide predictable, natural-looking, long-lasting results. Adverse reactions after hyaluronic acid injections tend to be mild or moderate and rather temporary. However, as with all injected or implanted biomaterials, severe adverse events can occur and patients must be fully informed of potential risks prior to undergoing treatment. A panel of experts from Germany (D), Austria (A) and Switzerland (CH) developed recommendations, and this study provides the 'DACH Consensus Recommendations' from this group specifically on the use of hyaluronic acid fillers. The aim is to help clinicians recognize potential risks and to provide guidance on how best to treat adverse events if they arise. Contraindications to hyaluronic acid fillers are also detailed, and ways to prevent adverse events occurring are discussed. Hyaluronic acid-based products are claimed to be very close to an ideal tissue augmentation agent; nevertheless, profound medical, anatomical and product knowledge are of paramount importance to minimize the occurrence of adverse reactions.

Precaution for volume conduction in rodent cortical electroencephalography using high-density polyimide-based microelectrode arrays on the skull.

In humans, significant progress has been made to link spatial changes in electroencephalographic (EEG) spectral density, connectivity strength, and phase-amplitude modulation to neurological, physiological, and psychological correlates. In contrast, standard rodent EEG techniques employ only few electrodes, which results in poor spatial resolution. Recently, a technique was developed to overcome this limitation in mice. This technique was based on a polyimide-based microelectrode (PBM) array applied on the mouse skull, maintaining a significant number of electrodes with consistent contact, electrode impedance, and mechanical stability. The present study built on this technique by extending it to rats. Therefore, a similar PBM array, but adapted to rats, was designed and fabricated. In addition, this array was connected to a wireless EEG headstage, allowing recording in untethered, freely moving rats. The advantage of a high-density array relies on the assumption that the signal recorded from the different electrodes is generated from distinct sources, i.e., not volume-conducted. Therefore, the utility and validity of the array were evaluated by determining the level of synchrony between channels due to true synchrony or volume conduction during basal vigilance states and following a subanesthetic dose of ketamine. Although the PBM array allowed recording with high signal quality, under both drug and drug-free conditions, high synchronization existed due to volume conduction between the electrodes even in the higher spectral frequency range. Discrimination existed only between frontally and centrally/distally grouped electrode pairs. Therefore, caution should be used in interpreting spatial data obtained from high-density PBM arrays in rodents.

Evaluation of two-dimensional intraoperative neuromonitoring for predicting urinary and anorectal function after rectal cancer surgery.

PURPOSE: The aim of this study was to compare the results of two-dimensional intraoperative neuromonitoring (IONM) with the postoperative urinary and anorectal function of rectal cancer patients. METHODS: A consecutive series of 35 patients undergoing low anterior resection were investigated prospectively. IONM was performed with electric stimulations of the pelvic splanchnic nerves under simultaneous manometry of the bladder and electromyography (EMG) of the internal anal sphincter (IAS). Urinary and anorectal function were evaluated preoperatively and at follow-up by standardized questionnaires, digital rectal examination scoring system, and long-term catheterization rate. RESULTS: The rate of postoperative newly developed bladder dysfunction was 17 %. IONM with bladder manometry had a sensitivity of 100 %, specificity of 96 %, positive predictive value of 83 %, negative predictive value of 100 %, and overall accuracy of 97 %, respectively. The proportion of patients with severely impaired anorectal function at follow-up was 8 %. The sensitivity, specificity, and positive and negative predictive values for IONM with EMG of the IAS were, respectively, 100, 96, 67, and 100 % with an accuracy of 96 %. The degree of agreement for IONM with EMG of the IAS was good for anorectal function (к = 0.780) and poor for urinary function (к = 0.119). IONM with bladder manometry yielded a very good degree of agreement for urinary function (к = 0.891) and a fair agreement for anorectal function (к = 0.336). CONCLUSIONS: The two-dimensional IONM method is suitable for verification of bladder and IAS innervation. Accurate prediction of urinary and anorectal function necessitates both bladder manometry and EMG of the IAS.

Effect of feature-selective attention on neuronal responses in macaque area MT.

Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color).

Continuous intraoperative monitoring of autonomic nerves during low anterior rectal resection: an innovative approach for observation of functional nerve integrity in pelvic surgery.

PURPOSE: The aim of this study was to develop a methodological setup for continuous intraoperative neuromonitoring with intent to improve nerve-sparing pelvic surgery. METHODS: Fourteen pigs underwent low anterior rectal resection. Continuous stimulation of pelvic autonomic nerves was carried out with a newly developed tripolar surface electrode during lateral, anterolateral, and anterior mesorectal dissection. Neuromonitoring was performed under electromyography of the autonomic innervated internal anal sphincter. RESULTS: Continuous neuromonitoring resulted in significantly increased electromyographic amplitudes of the internal anal sphincter, confirming intact innervation throughout the whole dissection in each animal (median 0.9 µV, interquartile range 0.5; 1.5 vs. median 3.4 µV, interquartile range 2.1; 4.7) (p < 0.001). The median dissection time in each animal was 10 min within a median number of ten (range 8-13) tripolar electric stimulations. CONCLUSION: The present study is the first to demonstrate that continuous intraoperative monitoring of pelvic autonomic nerves during low anterior rectal resection is feasible.

Online signal processing of internal anal sphincter activity during pelvic autonomic nerve stimulation: a new method to improve the reliability of intra-operative neuromonitoring signals.

AIM: Intra-operative neuromonitoring is increasingly applied in several surgical disciplines and has been introduced to facilitate pelvic autonomic nerve preservation. Nevertheless, it has been considered a questionable tool for the minimization of risk, as the results are variable and might be misleading. The aim of the present experimental study was to develop an intra-operative neuromonitoring system with improved reliability for monitoring pelvic autonomic nerve function. METHOD: Fifteen pigs underwent low anterior rectal resection with pelvic autonomic nerve preservation. Intra-operative neuromonitoring was performed under autonomic nerve stimulation with observation of electromyographic signals of the internal anal sphincter and bladder manometry. As the internal anal sphincter frequency spectrum during stimulation was found to be mainly in the range of 5-20 Hz, intra-operative neuromonitoring signals were postoperatively processed by implementation of matching band pass filters. RESULTS: In 10 preliminary experiments, signal processing was performed offline in the postoperative analysis. Of 163 stimulations intra-operatively assessed by the surgeon as positive responses, 135 (83%) were confirmed after signal processing. In the following five consecutive experiments intra-operative online signal processing was realized and demonstrated reliable intra-operative neuromonitoring signals of internal anal sphincter activity with significant increase during pelvic autonomic nerve stimulation [0.5 µV (interquartile range = 0.3-0.7) vs 4.8 µV (interquartile range = 2.5-7.5); P < 0.001]. CONCLUSION: Online signal processing of internal anal sphincter activity aids reliable identification of pelvic autonomic nerves with potential for improvement of intra-operative neuromonitoring in pelvic surgery.

Selective pelvic autonomic nerve stimulation with simultaneous intraoperative monitoring of internal anal sphincter and bladder innervation.

BACKGROUND: Pelvic autonomic nerve preservation avoids postoperative functional disturbances. The aim of this feasibility study was to develop a neuromonitoring system with simultaneous intraoperative verification of internal anal sphincter (IAS) activity and intravesical pressure. METHODS: 14 pigs underwent low anterior rectal resection. During intermittent bipolar electric stimulation of the inferior hypogastric plexus (IHP) and the pelvic splanchnic nerves (PSN), electromyographic signals of the IAS and manometry of the urinary bladder were observed simultaneously. RESULTS: Stimulation of IHP and PSN as well as simultaneous intraoperative monitoring could be realized with an adapted neuromonitoring device. Neurostimulation resulted in either bladder or IAS activation or concerted activation of both. Intravesical pressure increase as well as amplitude increase of the IAS neuromonitoring signal did not differ significantly between stimulation of IHP and PSN [6.0 cm H(2)O (interquartile range [IQR] 3.5-9.0) vs. 6.0 cm H(2)O (IQR 3.0-10.0) and 12.1 µV (IQR 3.0-36.7) vs. 40.1 µV (IQR 9.0-64.3)] (p > 0.05). CONCLUSIONS: Pelvic autonomic nerve stimulation with simultaneous intraoperative monitoring of IAS and bladder innervation is feasible. The method may enable neuromonitoring with increasing selectivity for pelvic autonomic nerve preservation.

Visual response properties of neurons in cortical areas MT and MST projecting to the dorsolateral pontine nucleus or the nucleus of the optic tract in macaque monkeys.

Neurons in cortical medial temporal area (MT) and medial superior temporal area (MST) projecting to the dorsolateral pontine nucleus (DLPN) and/or to the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN) were identified by antidromic electrical stimulation in five macaque monkeys. Neurons projecting to either target were located in close proximity to each other, and in all subregions of MT and MST sampled. Only a small percentage of the antidromically identified projection neurons (4.4%) sent branches to both the NOT-DTN and the DLPN. Antidromic latencies of neurons projecting to the NOT-DTN (0.9-6 ms, median 2.1 ms) and to the DLPN (0.8-5 ms, median 2.0 ms) did not differ significantly. Visual response properties of the neurons antidromically activated from either site did not differ significantly from those of cells that were not so activated. On the population level only neurons activated from the NOT-DTN had a clear preference for ipsiversive stimulus movement, whereas the neurons activated from the DLPN and neurons not antidromically activated from either target had no common directional preference. These results are discussed in terms of specification of cortico-subcortical connections and with regard to pathways underlying slow eye movements in different visuomotor behaviours.

Retinal projections to the accessory optic system in pigmented and albino ferrets (Mustela putorius furo).

We investigated if a reduced specificity of the retinal projection to the accessory optic system might be responsible for the loss of direction selectivity in the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN) and, in consequence of this, the optokinetic deficits in albino ferrets. Under electrophysiological control we performed dual tracer injections into the NOT-DTN and the medial terminal nucleus (MTN). Retrogradely labelled ganglion cells were found in the visual streak, the dorsal, and the ventral retina both after injections into the NOTDTN and the MTN indicating that both nuclei receive input from the same retinal regions. The distribution and spacing of labelled ganglion cells did not differ between pigmented and albino ferrets. However, retinal ganglion cells projecting simultaneously to both the NOT-DTN and the MTN occurred only in albino ferrets. These results suggest that a reduced specificity of the projection pattern of direction specific ganglion cells may contribute to the loss of direction selectivity in the NOT-DTN in albino ferrets.

Sensitivity to relative disparity in early visual cortex of pigmented and albino ferrets.

To investigate binocular interactions as the neuronal substrate for disparity sensitivity in the ferret (Mustela putorius furo), we measured the effects of relative horizontal disparities on responses of neurons in areas 17 and 18 of the visual cortex. Stimulation by moving bars and sinusoidal gratings showed that about half of our sample in pigmented ferrets was sensitive to relative horizontal disparity. This also included many neurons, which were classified as only monocularly activated when testing either eye alone. However, the tuning width was about two or three times coarser (median tuning width 4 degrees of visual angle) than that in the cat. In albino ferrets, only 8% of the neurons in the early visual cortex displayed some sort of disparity-dependent binocular interactions, but none could be clearly identified as relative disparity-coding neuron.

Neuronal firing rate, inter-neuron correlation and synchrony in area MT are correlated with directional choices during stimulus and reward expectation.

Sensation, memories, and predictions contribute to choices in everyday life, and their relative impact should change with task constraints. To investigate how the impact from sensory cortex on decision making varies with task constraints we trained macaque monkeys in a direction discrimination task where they could maximize reward by waiting for sensory visual information early in a trial, while focusing on memory and reward prediction as a trial progressed. The task constraints caused animals to indicate decisions in complete absence of visual motion stimuli (stimulus independent decisions), as 25% of the trials were 'no stimulus' trials. On 'no stimulus' trials reward delivery depended on the current decision in relation to the decision history. Stimulus independent decisions occurred during an epoch when a stimulus could in principle have been presented, or afterwards when stimuli could not occur anymore. Stimulus independent decisions were significantly different during these two periods. Reward exploitation was more efficient late in the trial, but it was not associated with systematic activity changes in directionally selective neurons in area MT. Conversely, systematic changes of neuronal activity and firing rate correlation in directionally selective middle temporal area (MT) neurons were restricted to a short time period before early decisions. Changing task constraints in the course of a single trial thus determines how neurons in sensory areas contribute to decision making.

Deficits of visual motion perception and optokinetic nystagmus after posterior suprasylvian lesions in the ferret (Mustela putorius furo).

We recently described an area in the ferret posterior suprasylvian (PSS) cortex characterized by a high proportion of direction selective neurons. To answer the question whether area PSS subserves functions similar to cat posteromediolateral suprasylvian area (PMLS) and monkey medial temporal area (MT) we investigated the contribution of area PSS to visual motion perception and optokinetic nystagmus. Ferrets were tested on global motion detection before and after bilateral lesions involving area PSS and control lesions of other extrastriate visual areas. Following PSS lesions motion coherence thresholds were significantly increased both in pigmented and albino ferrets, whereas control lesions sparing PSS did not affect visual motion perception. Optokinetic nystagmus was strongly reduced to absent after PSS lesions. These results indicate that area PSS is crucial for global motion processing in the ferret and in that sense may be functionally equivalent to PMLS in the cat and area MT in the monkey.

Transcutaneous sacral nerve stimulation for intraoperative verification of internal anal sphincter innervation.

BACKGROUND: The current standard for pelvic intraoperative neuromonitoring (pIONM) is based on intermittent direct nerve stimulation. This study investigated the potential use of transcutaneous sacral nerve stimulation for non-invasive verification of pelvic autonomic nerves. METHODS: A consecutive series of six pigs underwent low anterior rectal resection. For transcutaneous sacral nerve stimulation, an array of ten electrodes (cathodes) was placed over the sacral foramina (S2 to S4). Anodes were applied on the back, right and left thigh, lower abdomen, and intra-anally. Stimulation using the novel method and current standard were performed at different phases of the experiments under electromyography of the autonomic innervated internal anal sphincter (IAS). KEY RESULTS: Transcutaneous stimulation induced increase of IAS activity could be observed in each animal under specific cathode-anode configurations. Out of 300 tested configurations, 18 exhibited a change in the IAS activity correlated with intentional autonomic nerve damage. The damage resulted in a significant decrease of the relative area under the curve of the IAS frequency spectrum (P<.001). Comparison of the IAS spectra under transcutaneous and direct stimulation revealed no significant difference (after rectal resection: median 5.99 µV•Hz vs 7.78 µV•Hz, P=.12; after intentional nerve damage: median -0.27 µV•Hz vs 3.35 µV•Hz, P=.29). CONCLUSIONS AND INFERENCES: Non-invasive selective transcutaneous sacral nerve stimulation could be used for verification of IAS innervation.

Motion perception in rats (Rattus norvegicus sp.): deficits in albino Wistar rats compared to pigmented Long-Evans rats.

Motion perception was tested in pigmented Long-Evans and albino Wistar rats (Rattus norvegicus sp.) using moving random dot patterns. Pigmented as well as albino rats could distinguish a fully coherently moving pattern from dynamic noise. However, motion coherence thresholds were significantly lower in pigmented compared to albino rats (12% and 30% coherence, respectively). These results indicate that pigmented rats have well developed motion coherence perception, whereas albino rats are severely impaired but not motion blind.

Motion perception deficits in albino ferrets (Mustela putorius furo).

Albino ferrets contrary to their pigmented conspecifics show no optokinetic nystagmus. Therefore, in this study motion perception was compared between pigmented and albino ferrets (Mustela putorius furo) trained to discriminate between coherently moving random dot patterns and dynamic noise stimuli in a two-alternative forced choice task. Fully coherently versus incoherently moving patterns could be distinguished by ferrets of both phenotypes. Motion coherence thresholds, however, were significantly higher in albinos. These results indicate that albino ferrets are not motion blind as could be expected from their total lack of optokinetic reactions. However, they are severely impaired in global motion perception.

The role of the human thalamus in processing corollary discharge.

Corollary discharge signals play an important role in monitoring self-generated movements to guarantee spatial constancy. Recent work in macaques suggests that the thalamus conveys corollary discharge information of upcoming saccades passing from the superior colliculus to the frontal eye field. The present study aimed to investigate the involvement of the thalamus in humans by assessing the effect of thalamic lesions on the processing of corollary discharge information. Thirteen patients with selective thalamic lesions and 13 healthy age-matched control subjects performed a saccadic double-step task in which retino-spatial dissonance was induced, i.e. the retinal vector of the second target and the movement vector of the second saccade were different. Thus, the subjects could not rely on retinal information alone, but had to use corollary discharge information to correctly perform the second saccade. The amplitudes of first and second saccades were significantly smaller in patients than in controls. Five thalamic lesion patients showed unilateral deficits in using corollary discharge information, as revealed by asymmetries compared with the other patients and controls. Three patients with lateral thalamic lesions including the ventrolateral nucleus (VL) were impaired contralaterally to the side of damage and one patient with a lesion in the mediodorsal thalamus (MD) was impaired ipsilaterally to the lesion. The largest asymmetry was found in a patient with a bilateral thalamic lesion. The results provide evidence for a thalamic involvement in the processing of corollary discharge information in humans, with a potential role of both the VL and MD nuclei.

Physiological Characterization of Pretectal Neurons Projecting to the Láteral Geniculate Nucleus in the Cat.

Single neurons in the pretectal nucleus of the optic tract and posterior pretectal nucleus were extracellularly recorded in anaesthetized cats and tested for antidromic activation after electrical stimulation of the ipsilateral dorsal lateral geniculate nucleus. Cells were further characterized by their response latencies to electrical stimulation of the optic nerve head and the optic chiasm, and by responses to various visual stimuli. 46 out of 188 neurons (24%) were antidromically activated from the lateral geniculate nucleus at response latencies of 0.6 - 2.6 ms. They had low spontaneous activities and preferred fast-moving visual stimuli. 29 of the antidromically activated neurons (63%) could be activated from the optic chiasm with response latencies of 4 - 10 ms. Together with the mean conduction time of 0.8 ms between the optic nerve head and the optic chiasm, this indicates that they receive an indirect retinal input via fast-conducting Y-fibres. Sometimes antidromically activated neurons spontaneously showed irregular burst activity. During unidirectional stimulation with a large moving visual stimulus, burst activity became more regular, and interburst intervals and the duration of single bursts decreased. After the stimulus was stopped, interburst intervals slowly increased until prestimulation activity was restored. The response properties of these neurons could reflect the transfer of saccade-related visual as well as oculomotor signals through the pretectum to the visual thalamus.

A correlation between receptive field properties and morphological structures in the pretectum of the cat.

Retinal terminals in the pretectum were labelled by anterograde axonal transport of horseradish peroxidase (HRP) after injecting the enzyme into one eye. Pretectal neurons were retrogradely labelled by HRP-injections into the dorsal cap of the inferior olive. Electrophysiological recordings were performed in the same animal. This procedure showed that direction-selective neurons in the nucleus of the optic tract (NOT) projecting to the dorsal cap of the inferior olive lie dorsal and lateral to the retinal terminal clusters. Direction-unselective neurons sensitive to high stimulus velocities (jerk-neurons) were localized within the areas of retinal terminal clusters. Both jerk-neurons and retinal terminal clusters never overlapped with retrogradely labelled neurons. Latency measurements to stimulation of the optic chiasm (OX) confirmed a monosynaptic W-cell projection to the direction-selective NOT cells and indicated a predominantly monosynaptic Y-cell projection to the jerk-neurons.

OKN-related neurons in the rat nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system receive a direct cortical input.

It has been previously assumed that the asymmetry of the monocular optokinetic nystagmus (OKN) of lateral-eyed mammals is caused by an absence of visual cortex projections to directional selective neurons in the pretectal nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT-DTN). In contrast to this generally accepted hypothesis, we present multiple evidence that OKN-related neurons in the rat NOT-DTN in fact do receive input from the visual cortex. We studied the corticofugal projection to NOT-DTN physiologically, with extracellular single unit recording and electrical stimulation of the optic chiasma and the visual cortex, and anatomically, using retrograde and anterograde tracing techniques. In particular we focussed our attention on the NOT-DTN neurons, which control eye movements during OKN. All OKN-related NOT-DTN cells were activated after optic chiasma stimulation. Forty-five percent of these neurons were also activated after stimulation of the visual cortex (VC). The majority of neurons activated from VC (80%) also responded to monocular stimulation of either eye. On the contrary, most of the neurons that responded to stimulation of the contralateral eye only were not activated from VC. After injection of fluorescent latex microspheres into the NOT-DTN, retrogradely labeled neurons were found in areas 17, 18, and 18A of the visual cortex. Phaseolus vulgaris leucoagglutinin injected into the visual cortex anterogradely labeled fibres and terminals throughout the NOT-DTN complex. Labeled boutons were found in close proximity to OKN-related NOT-DTN cells, selectively stained after horseradish peroxidase (HRP) injections into the inferior olive. Our results demonstrate that NOT-DTN cells in the rat, which are involved in the generation of horizontal OKN, receive a direct input from the ipsilateral visual cortex.

Glia cells of the monkey retina. I. Astrocytes.

Morphology and distribution of retinal astrocytes have been studied in macaque monkeys by immunocytochemical localization of glial fibrillary acidic protein (GFAP). With the exception of the fovea and the far periphery, astrocytes are ubiquitous in the nerve fiber layer (NFL) and the ganglion cell layer (GCL) of the monkey retina. The morphology of NFL astrocytes changes gradually, from star-shaped in the periphery to bipolar close to the optic disc. By contrast, GCL astrocytes maintain their star-shaped appearance throughout the retina. Astrocytes are unevenly distributed in the monkey retina, showing the highest concentration around the optic disc, and particularly low densities in the perifoveal region and the far periphery. The fovea proper is devoid of astrocytes. Employing high-resolution confocal microscopy, we could demonstrate that astrocytes form manifold contacts to blood vessels. In addition, bundles of NFL astrocyte processes are co-localized with axon bundles, individual astrocytes forming contacts to several axon bundles. In contrast, a similar affinity of astrocytes to ganglion cell somata was never observed. Thus, our data confirm and extend the current knowledge of morphology and putative function of astrocytes in mammalian and especially the primate retina.