Is off-frequency overshoot caused by adaptation of suppression?

This study is concerned with the mechanism of off-frequency overshoot. Overshoot refers to the phenomenon whereby a brief signal presented at the onset of a masker is easier to detect when the masker is preceded by a “precursor” sound (which is often the same as the masker). Overshoot is most prominent when the masker and precursor have a different frequency than the signal (henceforth referred to as “off-frequency overshoot”). It has been suggested that off-frequency overshoot is based on a similar mechanism as “enhancement,” which refers to the perceptual pop-out of a signal after presentation of a precursor that contains a spectral notch at the signal frequency; both have been proposed to be caused by a reduction in the suppressive masking of the signal as a result of the adaptive effect of the precursor (“adaptation of suppression”). In this study, we measured overshoot, suppression, and adaptation of suppression for a 4-kHz sinusoidal signal and a 4.75-kHz sinusoidal masker and precursor, using the same set of participants. We show that, while the precursor yielded strong overshoot and the masker produced strong suppression, the precursor did not appear to cause any reduction (adaptation) of suppression. Predictions based on an established model of the cochlear input–output function indicate that our failure to obtain any adaptation of suppression is unlikely to represent a false negative outcome. Our results indicate that off-frequency overshoot and enhancement are likely caused by different mechanisms. We argue that overshoot may be due to higher-order perceptual factors such as transient masking or attentional diversion, whereas enhancement may be based on mechanisms similar to those that generate the Zwicker tone

Can Acting Out Online Improve Adolescents’ Well-Being During Contact Restrictions? A First Insight Into the Dysfunctional Role of Cyberbullying and the Need to Belong in Well-Being During COVID-19 Pandemic-Related Contact Restrictions

Connecting with peers online to overcome social isolation has become particularly important during the pandemic-related school closures across many countries. In the context of contact restrictions, feelings of isolation and loneliness are more prevalent and the regulation of these negative emotions to maintain a positive well-being challenges adolescents. This is especially the case for those individuals who might have a high need to belong and difficulties in emotional competences. The difficult social situation during contact restrictions, more time for online communication and maladaptive emotion regulation might lead to aggressive communication patterns in the form of cyberbullying perpetration. In an online study with N = 205 adolescents aged 14–19 (M = 15.83, SD = 1.44; 57% girls), we assessed the frequency of online and offline contacts, need to belong, emotion regulation problems, feelings of loneliness, and cyberbullying perpetration as predictors of adolescents’ well-being. In particular, we explored whether cyberbullying perpetration might function as a maladaptive strategy to deal with feelings of loneliness and therefore predicts well-being. This effect was expected to be stronger for those with a higher need to belong and with higher emotion regulation problems. Results of a hierarchical regression analysis revealed that well-being was significantly predicted by less emotion regulation difficulties, less feeling isolated and more cyberbullying perpetration. We also tested whether the need to belong or emotion regulation problems moderated the association between cyberbullying and well-being. While the results for emotion regulation problems were not significant, the moderation effect for the need to belong was significant: For students with a high need to belong, well-being was more strongly related to cyberbullying perpetration than for students with a medium need to belong. For students with a low need to belong, cyberbullying was not significantly associated with well-being. That cyberbullying perpetration predicted well-being positively is rather surprising in the light of previous research showing negative psychosocial outcomes also for cyberbullying perpetrators. The moderation analysis provides a hint at underlying processes: In times of distance learning and contact restrictions, cyberbullying may be a way of coming into contact with others and to regulate loneliness maladaptively

Regulation of auditory plasticity during critical periods and following hearing loss

Sensory input has profound effects on neuronal organization and sensory maps in the brain. The mechanisms regulating plasticity of the auditory pathway have been revealed by examining the consequences of altered auditory input during both developmental critical periods—when plasticity facilitates the optimization of neural circuits in concert with the external environment—and in adulthood—when hearing loss is linked to the generation of tinnitus. In this review, we summarize research identifying the molecular, cellular, and circuit-level mechanisms regulating neuronal organization and tonotopic map plasticity during developmental critical periods and in adulthood. These mechanisms are shared in both the juvenile and adult brain and along the length of the auditory pathway and serve to regulate disinhibitory networks, synaptic structure and function, as well as structural barriers to plasticity. Regulation of plasticity also involves both neuromodulatory circuits, which link plasticity with learning and attention, as well as ascending and descending auditory circuits, which link the auditory cortex and lower structures. Further work identifying the interplay of molecular and cellular mechanisms associating hearing loss induced plasticity with brain changes observed as part of tinnitus should advance strategies to treat tinnitus by molecularly modulating plasticity

The neural substrate for binaural masking level differences in the auditory cortex

The binaural masking level difference (BMLD) is a phenomenon whereby a signal that is identical at each ear (S0), masked by a noise that is identical at each ear (N0), can be made 12–15 dB more detectable by inverting the waveform of either the tone or noise at one ear (Sπ, Nπ). Single-cell responses to BMLD stimuli were measured in the primary auditory cortex of urethane-anesthetized guinea pigs. Firing rate was measured as a function of signal level of a 500 Hz pure tone masked by low-passed white noise. Responses were similar to those reported in the inferior colliculus. At low signal levels, the response was dominated by the masker. At higher signal levels, firing rate either increased or decreased. Detection thresholds for each neuron were determined using signal detection theory. Few neurons yielded measurable detection thresholds for all stimulus conditions, with a wide range in thresholds. However, across the entire population, the lowest thresholds were consistent with human psychophysical BMLDs. As in the inferior colliculus, the shape of the firing-rate versus signal-level functions depended on the neurons' selectivity for interaural time difference. Our results suggest that, in cortex, BMLD signals are detected from increases or decreases in the firing rate, consistent with predictions of cross-correlation models of binaural processing and that the psychophysical detection threshold is based on the lowest neural thresholds across the population

Neurons in the inferior colliculus of the rat show stimulus-specific adaptation for frequency, but not for intensity

Electrophysiological and psychophysical responses to a low-intensity probe sound tend to be suppressed by a preceding high-intensity adaptor sound. Nevertheless, rare low-intensity deviant sounds presented among frequent high-intensity standard sounds in an intensity oddball paradigm can elicit an electroencephalographic mismatch negativity (MMN) response. This has been taken to suggest that the MMN is a correlate of true change or “deviance” detection. A key question is where in the ascending auditory pathway true deviance sensitivity first emerges. Here, we addressed this question by measuring low-intensity deviant responses from single units in the inferior colliculus (IC) of anesthetized rats. If the IC exhibits true deviance sensitivity to intensity, IC neurons should show enhanced responses to low-intensity deviant sounds presented among high-intensity standards. Contrary to this prediction, deviant responses were only enhanced when the standards and deviants differed in frequency. The results could be explained with a model assuming that IC neurons integrate over multiple frequency-tuned channels and that adaptation occurs within each channel independently. We used an adaptation paradigm with multiple repeated adaptors to measure the tuning widths of these adaption channels in relation to the neurons’ overall tuning widths

Neuroimaging paradigms for tonotopic mapping (II): the influence of acquisition protocol.

AbstractNumerous studies on the tonotopic organisation of auditory cortex in humans have employed a wide range of neuroimaging protocols to assess cortical frequency tuning. In the present functional magnetic resonance imaging (fMRI) study, we made a systematic comparison between acquisition protocols with variable levels of interference from acoustic scanner noise. Using sweep stimuli to evoke travelling waves of activation, we measured sound-evoked response signals using sparse, clustered, and continuous imaging protocols that were characterised by inter-scan intervals of 8.8, 2.2, or 0.0s, respectively. With regard to sensitivity to sound-evoked activation, the sparse and clustered protocols performed similarly, and both detected more activation than the continuous method. Qualitatively, tonotopic maps in activated areas proved highly similar, in the sense that the overall pattern of tonotopic gradients was reproducible across all three protocols. However, quantitatively, we observed substantial reductions in response amplitudes to moderately low stimulus frequencies that coincided with regions of strong energy in the scanner noise spectrum for the clustered and continuous protocols compared to the sparse protocol. At the same time, extreme frequencies became over-represented for these two protocols, and high best frequencies became relatively more abundant. Our results indicate that although all three scanning protocols are suitable to determine the layout of tonotopic fields, an exact quantitative assessment of the representation of various sound frequencies is substantially confounded by the presence of scanner noise. In addition, we noticed anomalous signal dynamics in response to our travelling wave paradigm that suggest that the assessment of frequency-dependent tuning is non-trivially influenced by time-dependent (hemo)dynamics when using sweep stimuli

Understanding Pitch Perception as a Hierarchical Process with Top-Down Modulation

Pitch is one of the most important features of natural sounds, underlying the perception of melody in music and prosody in speech. However, the temporal dynamics of pitch processing are still poorly understood. Previous studies suggest that the auditory system uses a wide range of time scales to integrate pitch-related information and that the effective integration time is both task- and stimulus-dependent. None of the existing models of pitch processing can account for such task- and stimulus-dependent variations in processing time scales. This study presents an idealized neurocomputational model, which provides a unified account of the multiple time scales observed in pitch perception. The model is evaluated using a range of perceptual studies, which have not previously been accounted for by a single model, and new results from a neurophysiological experiment. In contrast to other approaches, the current model contains a hierarchy of integration stages and uses feedback to adapt the effective time scales of processing at each stage in response to changes in the input stimulus. The model has features in common with a hierarchical generative process and suggests a key role for efferent connections from central to sub-cortical areas in controlling the temporal dynamics of pitch processing

Apheresis therapies for NMOSD attacks A retrospective study of 207 therapeutic interventions

Objective To analyze whether 1 of the 2 apheresis techniques, therapeutic plasma exchange (PE) or immunoadsorption (IA), is superior in treating neuromyelitis optica spectrum disorder (NMOSD) attacks and to identify predictive factors for complete remission (CR). Methods This retrospective cohort study was based on the registry of the German Neuromyelitis Optica Study Group, a nationwide network established in 2008. It recruited patients with neuromyelitis optica diagnosed according to the 2006 Wingerchuk criteria or with aquaporin-4 (AQP4-ab)-antibody-seropositive NMOSD treated at 6 regional hospitals and 16 tertiary referral centers until March 2013. Besides descriptive data analysis of patient and attack characteristics, generalized estimation equation (GEE) analyses were applied to compare the effectiveness of the 2 apheresis techniques. A GEE model was generated to assess predictors of outcome. Results Two hundred and seven attacks in 105 patients (87% AQP4-ab-antibody seropositive) were treated with at least 1 apheresis therapy. Neither PE nor IA was proven superior in the therapy of NMOSD attacks. CR was only achieved with early apheresis therapy. Strong predictors for CR were the use of apheresis therapy as first-line therapy (OR 12.27, 95% CI: 1.04-144.91, p = 0.047), time from onset of attack to start of therapy in days (OR 0.94, 95% CI: 0.89-0.99, p = 0.014), the presence of AQP4-abantibodies (OR 33.34, 95% CI: 1.76-631.17, p = 0.019), and monofocal attack manifestation (OR 4.71, 95% CI: 1.03-21.62, p = 0.046). Conclusion: s Our findings suggest early use of an apheresis therapy in NMOSD attacks, particularly in AQP4-ab-seropositive patients. No superiority was shown for one of the 2 apheresis techniques

Lymphocyte Subsets Show Different Response Patterns to In Vivo Bound Natalizumab—A Flow Cytometric Study on Patients with Multiple Sclerosis

Natalizumab is an effective monoclonal antibody therapy for the treatment of relapsing- remitting multiple sclerosis (RRMS) and interferes with immune cell migration into the central nervous system by blocking the α4 subunit of very-late activation antigen-4 (VLA-4). Although well tolerated and very effective, some patients still suffer from relapses in spite of natalizumab therapy or from unwanted side effects like progressive multifocal leukoencephalopathy (PML). In search of a routine-qualified biomarker on the effectiveness of natalizumab therapy we applied flow cytometry and analyzed natalizumab binding to α4 and α4 integrin surface levels on T-cells, B-cells, natural killer (NK) cells, and NKT cells from 26 RRMS patients under up to 72 weeks of therapy. Four-weekly infusions of natalizumab resulted in a significant and sustained increase of lymphocyte-bound natalizumab (p<0.001) which was paralleled by a significant decrease in detectability of the α4 integrin subunit on all lymphocyte subsets (p<0.001). We observed pronounced natalizumab accumulations on T and B cells at single measurements in all patients who reported clinical disease activity (n = 4). The natalizumab binding capacity of in vitro saturated lymphocytes collected during therapy was strongly diminished compared to treatment-naive cells indicating a therapy-induced reduction of α4. Summing up, this pilot study shows that flow cytometry is a useful method to monitor natalizumab binding to lymphocytes from RRMS patients under therapy. Investigating natalizumab binding provides an opportunity to evaluate the molecular level of effectiveness of natalizumab therapy in individual patients. In combination with natalizumab saturation experiments, it possibly even provides a means of studying the feasability of patient-tailored infusion intervals. A routine-qualified biomarker on the basis of individual natalizumab saturation on lymphocyte subsets might be an effective tool to improve treatment safety

The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation

The formation of the mitotic spindle is a complex process that requires massive cellular reorganization. Regulation by mitotic kinases controls this entire process. One of these mitotic controllers is Aurora A kinase, which is itself highly regulated. In this study, we show that the nuclear pore protein ALADIN is a novel spatial regulator of Aurora A. Without ALADIN, Aurora A spreads from centrosomes onto spindle microtubules, which affects the distribution of a subset of microtubule regulators and slows spindle assembly and chromosome alignment. ALADIN interacts with inactive Aurora A and is recruited to the spindle pole after Aurora A inhibition. Of interest, mutations in ALADIN cause triple A syndrome. We find that some of the mitotic phenotypes that we observe after ALADIN depletion also occur in cells from triple A syndrome patients, which raises the possibility that mitotic errors may underlie part of the etiology of this syndrome