Effects of Stimulus Rate and Periodicity on Auditory Cortical Entrainment to Continuous Sounds.

The neural mechanisms underlying the exogenous coding and neural entrainment to repetitive auditory stimuli have seen a recent surge of interest. However, few studies have characterized how parametric changes in stimulus presentation alter entrained responses. We examined the degree to which the brain entrains to repeated speech (i.e., /ba/) and nonspeech (i.e., click) sounds using phase-locking value (PLV) analysis applied to multichannel human electroencephalogram (EEG) data. Passive cortico-acoustic tracking was investigated in N = 24 normal young adults utilizing EEG source analyses that isolated neural activity stemming from both auditory temporal cortices. We parametrically manipulated the rate and periodicity of repetitive, continuous speech and click stimuli to investigate how speed and jitter in ongoing sound streams affect oscillatory entrainment. Neuronal synchronization to speech was enhanced at 4.5 Hz (the putative universal rate of speech) and showed a differential pattern to that of clicks, particularly at higher rates. PLV to speech decreased with increasing jitter but remained superior to clicks. Surprisingly, PLV entrainment to clicks was invariant to periodicity manipulations. Our findings provide evidence that the brain's neural entrainment to complex sounds is enhanced and more sensitized when processing speech-like stimuli, even at the syllable level, relative to nonspeech sounds. The fact that this specialization is apparent even under passive listening suggests a priority of the auditory system for synchronizing to behaviorally relevant signals.

Children with amblyaudia show less flexibility in auditory cortical entrainment to periodic non-speech sounds.

OBJECTIVE: We investigated auditory temporal processing in children with amblyaudia (AMB), a subtype of auditory processing disorder (APD), via cortical neural entrainment. DESIGN AND STUDY SAMPLES: Evoked responses were recorded to click-trains at slow vs. fast (8.5 vs. 14.9/s) rates in n = 14 children with AMB and n = 11 age-matched controls. Source and time-frequency analyses (TFA) decomposed EEGs into oscillations (reflecting neural entrainment) stemming from bilateral auditory cortex. RESULTS: Phase-locking strength in AMB depended critically on the speed of auditory stimuli. In contrast to age-matched peers, AMB responses were largely insensitive to rate manipulations. This rate resistance occurred regardless of the ear of presentation and in both cortical hemispheres. CONCLUSIONS: Children with AMB show less rate-related changes in auditory cortical entrainment. In addition to reduced capacity to integrate information between the ears, we identify more rigid tagging of external auditory stimuli. Our neurophysiological findings may account for domain-general temporal processing deficits commonly observed in AMB and related APDs behaviourally. More broadly, our findings may inform communication strategies and future rehabilitation programmes; increasing the rate of stimuli above a normal (slow) speech rate is likely to make stimulus processing more challenging for individuals with AMB/APD.

Dichotic listening deficits in amblyaudia are characterized by aberrant neural oscillations in auditory cortex.

OBJECTIVE: Children diagnosed with auditory processing disorder (APD) show deficits in processing complex sounds that are associated with difficulties in higher-order language, learning, cognitive, and communicative functions. Amblyaudia (AMB) is a subcategory of APD characterized by abnormally large ear asymmetries in dichotic listening tasks. METHODS: Here, we examined frequency-specific neural oscillations and functional connectivity via high-density electroencephalography (EEG) in children with and without AMB during passive listening of nonspeech stimuli. RESULTS: Time-frequency maps of these "brain rhythms" revealed stronger phase-locked beta-gamma (~35 Hz) oscillations in AMB participants within bilateral auditory cortex for sounds presented to the right ear, suggesting a hypersynchronization and imbalance of auditory neural activity. Brain-behavior correlations revealed neural asymmetries in cortical responses predicted the larger than normal right-ear advantage seen in participants with AMB. Additionally, we found weaker functional connectivity in the AMB group from right to left auditory cortex, despite their stronger neural responses overall. CONCLUSION: Our results reveal abnormally large auditory sensory encoding and an imbalance in communication between cerebral hemispheres (ipsi- to -contralateral signaling) in AMB. SIGNIFICANCE: These neurophysiological changes might lead to the functionally poorer behavioral capacity to integrate information between the two ears in children with AMB.

Subcortical rather than cortical sources of the frequency-following response (FFR) relate to speech-in-noise perception in normal-hearing listeners.

Scalp-recorded frequency-following responses (FFRs) reflect a mixture of phase-locked activity across the auditory pathway. FFRs have been widely used as a neural barometer of complex listening skills, especially speech-in noise (SIN) perception. Applying individually optimized source reconstruction to speech-FFRs recorded via EEG (FFREEG), we assessed the relative contributions of subcortical [auditory nerve (AN), brainstem/midbrain (BS)] and cortical [bilateral primary auditory cortex, PAC] source generators with the aim of identifying which source(s) drive the brain-behavior relation between FFRs and SIN listening skills. We found FFR strength declined precipitously from AN to PAC, consistent with diminishing phase-locking along the ascending auditory neuroaxis. FFRs to the speech fundamental (F0) were robust to noise across sources, but were largest in subcortical sources (BS > AN > PAC). PAC FFRs were only weakly observed above the noise floor and only at the low pitch of speech (F0≈100 Hz). Brain-behavior regressions revealed (i) AN and BS FFRs were sufficient to describe listeners' QuickSIN scores and (ii) contrary to neuromagnetic (MEG) FFRs, neither left nor right PAC FFREEG related to SIN performance. Our findings suggest subcortical sources not only dominate the electrical FFR but also the link between speech-FFRs and SIN processing in normal-hearing adults as observed in previous EEG studies.

Immunohistochemical Analysis of LGR5 and TROY Expression in Gastric Carcinogenesis Demonstrates an Inverse Trend

Background: Two of the Wnt signaling pathway target genes, tumor necrosis factor receptor family member (TROY) and leucine-rich G-protein coupled receptor (LGR5), are involved in the generation and maintenance of gastrointestinal epithelium. A negative modulatory role has recently been assigned to TROY, in this pathway. Here, we have examined their simultaneous expression in gastric carcinogenesis. Methods: Tumor and paired adjacent tissues of intestinal-type gastric cancer (GC) patients (n = 30) were evaluated for LGR5 and TROY expression by immunohistochemistry. The combination of the percentage of positively¬ stained cells and the intensity of staining was defined as the composite score and compared between groups. The obtained findings were re-evaluated in a mouse model. Results: TROY expression in the tumor tissue was significantly lower than that of the adjacent tissue (2.5 ± 0.9 vs. 3.3 ± 0.9, p = 0.004), which was coincident with higher LGR5 expression (3.6 ± 1.1 vs. 2.7 ± 0.9, p = 0.001). This observation was prominent at stages II/III of GC, leading to a statistically significant mean difference of expression between these two molecules (p = 0.005). In the H. pylori infected-mouse model, this inverse expression was observed in transition from early (8-16 w) to late (26-50 w) time points, post treatment (p = 0.002). Conclusion: Our data demonstrates an inverse trend between TROY down-regulation and LGR5 up-regulation in GC tumors, as well as in response to H. pylori infection in mice. These findings support a potential negative modulatory role for TROY on LGR5 expression.

Quantitative oculomotor findings in migrainous patients.

BACKGROUND: Neurotologic signs and symptoms, especially vestibular symptoms are common in migrainous patients. Involvement of the visual system in migrainures has received a great deal of attention in recent years, but the oculomotor part of the visual system has been largely ignored. The goal of this study was to investigate some parts of the central vestibular system using the oculomotor part of videonystagmographic evaluation, including spontaneous nystagmus, gaze-evoked nystagmus, smooth pursuit, saccade and optokinetic ystagmus interictally in migrainous patients. METHODS: In this case-control study, 30 patients with migraine and 38 healthy volunteers within the age range of 18-48 years old were included spontaneous nystagmus; gaze-evoked nystagmus in right, left and up sides, smooth pursuit, optokinetic nystagmus using three different velocities and saccade test performed in both groups. The data were analyzed using SPSS for Windows 18.0. RESULTS: Some parameters of gain and phase and also morphology of the smooth pursuit, velocity of the saccade and slow phase velocity of optokinetic were significantly different in migrainures, although the statistical differences of these parameters were not clinically important as they were in the normal range of a defined device. CONCLUSION: These results may suggest the presence of subtle otoneurologic abnormalities in migrainous patients that is probably due to the efficiency of oculomotor function with vestibulocerebellar origin.

Correlation between brain cortex metabolic and perfusion functions in subjective idiopathic tinnitus.

OBJECTIVES: Subjective tinnitus has associated with abnormal brain metabolism and perfusion found in functional imaging studies by fluorodeoxyglucose (FDG) and technetium99m (TC99m). But there is no study evaluating the association of brain metabolism and perfusion abnormalities in a group of these subjects. The aim of this study was to investigate if there is any significant correlation between the brain perfusion and metabolism abnormalities in subjects with tinnitus. MATERIALS AND METHODS: In this cross-sectional study, 52 patients were undergone TC99m-ECD single photon emission computerized tomography (SPECT) scan and F18-FDG positron emission tomography (PET). The results of PET and SPECT scanning were fused with MRI to accurate anatomical localization of abnormalities. The analysis was performed using Kendal's correlation, t-test and chi square. RESULTS: Assessing these 52 tinnitus subjects (containing 42 males [76.4%]) showed that a significant correlation was found between the brain metabolic function and perfusion (p value 0.001).