Spatiotemporal patterns of cortical activity with bilateral cochlear implants in congenital deafness.

Congenital deafness affects developmental processes in the auditory cortex. In this study, local field potentials (LFPs) were mapped at the cortical surface with microelectrodes in response to cochlear implant stimulation. LFPs were compared between hearing controls and congenitally deaf cats (CDCs). Pulsatile electrical stimulation initially evoked cortical activity in the rostral parts of the primary auditory field (A1). This progressed both in the approximate dorsoventral direction (along the isofrequency stripe) and in the rostrocaudal direction. The dorsal branch of the wavefront split into a caudal branch (propagating in A1) and another smaller one propagating rostrally into the AAF (anterior auditory field). After the front reached the caudal border of A1, a "reflection wave" appeared, propagating back rostrally. In total, the waves took approximately 13-15 ms to propagate along A1 and return back. In CDCs, the propagation pattern was significantly disturbed, with a more synchronous activation of distant cortical regions. The maps obtained from contralateral and ipsilateral stimulation overlapped in both groups of animals. Although controls showed differences in the latency-amplitude patterns, cortical waves evoked by contralateral and ipsilateral stimulation were more similar in CDCs. Additionally, in controls, LFPs with contralateral and ipsilateral stimulation were more similar in caudal A1 than in rostral A1. This dichotomy was lost in deaf animals. In conclusion, propagating cortical waves are specific for the contralateral ear, they are affected by auditory deprivation, and the specificity of the cortex for stimulation of the contralateral ear is reduced by deprivation.

Food-derived peptides with biological activity: from research to food applications.

Many peptides that are released in vitro or in vivo from animal or plant proteins are bioactive and have regulatory functions in humans beyond normal and adequate nutrition. Different health effects have been attributed to food-derived peptides, including antimicrobial properties, blood pressure-lowering (ACE inhibitory) effects, cholesterol-lowering ability, antithrombotic and antioxidant activities, enhancement of mineral absorption and/or bioavailability, cyto- or immunomodulatory effects, and opioid activities. Numerous products are already on the market or under development by food companies that exploit the potential of food-derived bioactive peptides and which ascribe scientifically evidenced health claims to consumption of these functional foods.

Cochlear implants: cortical plasticity in congenital deprivation.

Congenital auditory deprivation (deafness) leads to a dysfunctional intrinsic cortical microcircuitry. This chapter reviews these deficits with a particular emphasis on layer-specific activity within the primary auditory cortex. Evidence for a delay in activation of supragranular layers and reduction in activity in infragranular layers is discussed. Such deficits indicate the incompetence of the primary auditory cortex to not only properly process thalamic input and generate output within the infragranular layers, but also incorporate top-down modulations from higher order auditory cortex into the processing within primary auditory cortex. Such deficits are the consequence of a misguided postnatal development. Maturation of primary auditory cortex in deaf animals shows evidence of a developmental delay and further alterations in gross synaptic currents, spread of activation, and morphology of local field potentials recorded at the cortical surface. Additionally, degenerative changes can be observed. When hearing is initiated early in life (e.g., by chronic cochlear-implant stimulation), many of these deficits are counterbalanced. However, plasticity of the auditory cortex decreases with increasing age, so that a sensitive period for plastic adaptation can be demonstrated within the second to sixth months of life in the deaf cat. Potential molecular mechanisms of the existence of sensitive period are discussed. Data from animal research may be compared to electroencephalographic data obtained from cochlear-implanted congenitally deaf children. After cochlear implantation in humans, three phases of plastic adaptation can be observed: a fast one, taking place within the first few weeks after implantation, showing no sensitive period; a slower one, taking place within the first months after implantation (a sensitive period up to 4 years of age); and possibly a third, and the longest one, related to increasing activation of higher order cortical areas.

Ototoxic side-effects of the I(Ks)-channel blocker HMR1556.

The inhibitor of I(Ks)-channels, HMR1556, a potentially antiarrhythmic drug, might possess ototoxic side-effects. The I(Ks)-channels are not only expressed in the heart but also in the stria vascularis of the inner ear and in the dark cells of the vestibular organ. Therefore possible effects of HMR1556 on hearing were studied in cats. Thresholds and intensity function of the cochlear action potential (CAP) were used as criteria. In addition to effects of the drug on heart rate and ECG, a substantial elevation of hearing thresholds and a shift in CAP intensity functions were observed. There was a clear dose-effect relationship. The hearing impairment observed showed a tendency for recovery. It is concluded that inhibitors of I(Ks)-channels may generally exert ototoxic effects provided they can reach the cochlear spaces.

Intraoperative microelectrode recording for the delineation of subthalamic nucleus topography in Parkinson's disease.

BACKGROUND: The subthalamic nucleus (STN) as an effective target for deep brain stimulation (DBS) in advanced Parkinson's disease is functionally divided into the dorsolateral sensorimotor and the ventromedial limbic and associative parts. To implant electrodes for DBS close to the sensorimotor region is considered crucial for optimal motor benefit and for avoidance of potential cognitive and behavioral side effects. OBJECTIVE: The aim of this study was to determine whether the functional segregation of the STN is associated with distinct and region-specific neuronal activity patterns and action potential properties obtained by intraoperative microelectrode recordings. METHODS: In 12 Parkinson's disease patients, stepwise intraoperative microelectrode recordings were performed using five concentrically configured electrodes starting 10 mm above the calculated target point until the dorsal border of the substantia nigra. RESULTS: Based on autocorrelogram analysis of a total of 329 single units, we found a higher occurrence of oscillatory (P < 0.01) and bursty (P = 0.058) spike pattern in the dorsal versus the ventral STN. In contrast the ventral region was characterized by irregular firing neurons (P < 0.01). There were no significant differences in firing frequency, coefficient of variance, asymmetry index as well as spike form, duration, and amplitude. CONCLUSIONS: Among all parameters analyzed in the study, spike pattern is the only convenient electrophysiologic parameter for the differentiation of STN subregions in patients with Parkinson's disease. The autocorrelogram-based analysis of spike activity seems to be of certain value for the delineation of the dorsolateral STN and might therefore facilitate the precise electrode implantation for DBS.

Neuronal responses in cat inferior colliculus to combined acoustic and electric stimulation.

The present study explored the interactions of combined electric and acoustic stimulation (EAS) on neural responses in the central auditory system. Normal-hearing cats were implanted unilaterally with scala tympani electrodes. Two experimental approaches were used. First, in a forward-masking paradigm, single biphasic electric pulses were used as maskers, unmodulated acoustic tone bursts at the neuron's characteristic frequency (CF) were used as probes. Then, in a simultaneous-masking paradigm, the masking effects of acoustic tones (CF) on responses to single electric pulses (probes) were examined. In the second approach, we studied the effects of phase relationship between acoustic and electric stimulation. Sinusoidal amplitude-modulated (30 Hz) CF tones and electric sinusoids (30 Hz) were shifted in relative phase (0-270 degrees). For all experimental conditions, the levels of the two stimuli were changed systematically. Responses were recorded in the contralateral central nucleus of the inferior colliculus. Single neuron analyses of spike rate and thresholds demonstrated that combined EAS resulted in complex interactions that were strongly dependent on the relative level of the given stimulus modes. The amount of masking increased with masker level and decreased with probe level. At higher current levels, the masking effect of electric responses dominated the effect of acoustic responses. The degree of these general masking effects was highly influenced by the relative phase between the combined stimuli. It seems likely that such interactions of combined stimulation have perceptual consequences in human cochlear implant subjects with residual hearing.

Application of a corticosteroid (Triamcinolon) protects inner ear function after surgical intervention.

HYPOTHESIS: Opening of the inner ear during stapes surgery or cochlear implantation may result in trauma to inner ear structures and possible hearing loss. The dual aim of the present study was to evaluate the effectiveness of locally applied Triamcinolon* to protect the inner ear against surgically induced trauma and to exclude possible ototoxic effects. METHODS: In an animal model (guinea pig), a corticosteroid (Triamcinolon) was topically applied to the inner ear, either by extracochlear application and diffusion through the round window membrane or by direct intracochlear application via a cochleostomy. Physiological effects of the steroid were investigated by monitoring the hearing of steroid treated animals in comparison to control animals treated with Ringer solution instead of Triamcinolon. Thresholds as well as input/output functions (I/O function) of compound action potentials (CAPs) in response to auditory stimuli were determined before the cochleostomy and at specific intervals up to 4 weeks after application of Triamcinolon. RESULTS: Extracochlear application of Triamcinolon induced only minor shifts of mean CAP thresholds but significantly increased mean maximal amplitudes of I/O function 14 d after application. No detrimental effects on cochlear function were noted; thus, indicating absence of ototoxicity for extracochlear application in the concentrations used. After the surgical trauma of cochleostomy, CAP thresholds increased by 12.5 dB directly after surgery and by 15.8 dB at day 3. Amplitudes of CAPs diminished. Intracochlear application of Triamcinolon resulted in significantly enhanced recovery of CAP thresholds and amplitudes of I/O function from initial loss over a period of 4 weeks. CONCLUSIONS: From these results, we conclude that extracochlear topical application of Triamcinolon has no ototoxic effect in the concentrations that were used and that intracochlear application supports an increased recovery of cochlear functions after surgical trauma. Furthermore, the results indicate a protective effect of corticosteroids, partially preventing progressive loss of hearing after cochleostomy over a period of 4 weeks. Intracochlear application of Triamcinolon may be useful to prevent hearing loss after surgical intervention on the inner ear; however, clinical safety and efficacy remain to be proven in clinical studies.

Cytotoxic and allergenic potential of bioactive proteins and peptides.

This review article deals with the assessment of cytotoxic and allergenic potential of bioactive proteins and peptides. It is evident that 'novel' foods or nutraceuticals containing bioactive proteins and peptides must fulfill their proposed "health claim". Furthermore, there is a need to assess their potential to exert adverse effects before they can be made widely available to consumers. A brief overview of compounds (i.e. proteins and peptides of animal and plant origin) and mechanisms involved in cytotoxic and allergenic (adverse) reactions is given along with some recent results obtained from ongoing studies. There are numerous proteins and peptides of plant and animal origin that are known to exhibit cytotoxic effects. There is evidence that many cytotoxic compounds described in the literature exclusively affect malignant cells leading to the assumption that a cancer protective effect could exist for such bioactive proteins and peptides. All the constituents that are responsible for the allergenicity of foods (as well as of pollens) are proteinaceous in nature. Some protein breakdown products, i.e. peptide fragments, may conserve part of the allergenicity of the native protein and thus can also be considered as allergens. The molecular basis of IgE recognition underlying cow's milk protein allergy is described. Some results from studies on volunteers fed caseinophosphopeptides or potentially hypotensive milk protein hydrolysates illustrate the major difference between allergenicity and immunogenicity. The data presented on the relationship between the structure of food proteins and peptides and their allergenicity shows the difficulty in trying to assess the "non-allergenicity" of products derived from an allergenic source, even if the process used involved extensive hydrolysis of the native protein(s). A 'weight of evidence approach' for assessing the potential allergenicity of a novel protein with no history of prior allergenicity is also presented with regard to the current EU Regulations.

Cytochemical assessment of phosphopeptides derived from casein as potential ingredients for functional food.

Phosphopeptides derived from casein hydrolysis are suggested to have beneficial effects beyond their mere nutritive value by enhancing availability of dietary minerals, especially calcium, iron and zinc. Apart from a possible positive action the potential may exist for adverse effects that could impose restrictions to their widespread application in functional foods for human nutrition. In the present work, various case-inophosphopeptide (CPP) preparations were assessed using different human cell culture model systems in order to estimate their cytotoxic potential and their influence on epithelial properties and differentiation of human intestinal cells (Caco-2). The general cytotoxic potential of CPPs was tested using the AlphaTox NR assay. Structural and functional differentiation of intestinal Caco-2 cells was determined by measuring transepithelial electrical resistance and activity of brush border associated alkaline phosphatase over an extended cultivation period. No loss in cell viability with respect to membrane integrity could be detected, as uptake and retention of neutral red dye (AlphaTox assay) into HeLa cells was not affected by the presence of CPPs. Cytochemical assays conducted on epithelial cells (Caco-2) showed no disturbance of normal cell development and differentiation with respect to structural as well as functional differentiation markers. As all CPPs tested did not provoke any adverse effects in terms of cytotoxicity and showed no impairment of cell differentiation and monolayer integrity of human intestinal cells, it may be supposed that CPPs do not provoke a cytotoxic response in vivo in the cells assayed in the present study.