Brainstem speech encoding is dynamically shaped online by fluctuations in cortical α state.

Experimental evidence in animals demonstrates cortical neurons innervate subcortex bilaterally to tune brainstem auditory coding. Yet, the role of the descending (corticofugal) auditory system in modulating earlier sound processing in humans during speech perception remains unclear. Here, we measured EEG activity as listeners performed speech identification tasks in different noise backgrounds designed to tax perceptual and attentional processing. We hypothesized brainstem speech coding might be tied to attention and arousal states (indexed by cortical α power) that actively modulate the interplay of brainstem-cortical signal processing. When speech-evoked brainstem frequency-following responses (FFRs) were categorized according to cortical α states, we found low α FFRs in noise were weaker, correlated positively with behavioral response times, and were more "decodable" via neural classifiers. Our data provide new evidence for online corticofugal interplay in humans and establish that brainstem sensory representations are continuously yoked to (i.e., modulated by) the ebb and flow of cortical states to dynamically update perceptual processing.

Attention reinforces human corticofugal system to aid speech perception in noise.

Perceiving speech-in-noise (SIN) demands precise neural coding between brainstem and cortical levels of the hearing system. Attentional processes can then select and prioritize task-relevant cues over competing background noise for successful speech perception. In animal models, brainstem-cortical interplay is achieved via descending corticofugal projections from cortex that shape midbrain responses to behaviorally-relevant sounds. Attentional engagement of corticofugal feedback may assist SIN understanding but has never been confirmed and remains highly controversial in humans. To resolve these issues, we recorded source-level, anatomically constrained brainstem frequency-following responses (FFRs) and cortical event-related potentials (ERPs) to speech via high-density EEG while listeners performed rapid SIN identification tasks. We varied attention with active vs. passive listening scenarios whereas task difficulty was manipulated with additive noise interference. Active listening (but not arousal-control tasks) exaggerated both ERPs and FFRs, confirming attentional gain extends to lower subcortical levels of speech processing. We used functional connectivity to measure the directed strength of coupling between levels and characterize "bottom-up" vs. "top-down" (corticofugal) signaling within the auditory brainstem-cortical pathway. While attention strengthened connectivity bidirectionally, corticofugal transmission disengaged under passive (but not active) SIN listening. Our findings (i) show attention enhances the brain's transcription of speech even prior to cortex and (ii) establish a direct role of the human corticofugal feedback system as an aid to cocktail party speech perception.

Psychobiological Responses Reveal Audiovisual Noise Differentially Challenges Speech Recognition.

OBJECTIVES: In noisy environments, listeners benefit from both hearing and seeing a talker, demonstrating audiovisual (AV) cues enhance speech-in-noise (SIN) recognition. Here, we examined the relative contribution of auditory and visual cues to SIN perception and the strategies used by listeners to decipher speech in noise interference(s). DESIGN: Normal-hearing listeners (n = 22) performed an open-set speech recognition task while viewing audiovisual TIMIT sentences presented under different combinations of signal degradation including visual (AVn), audio (AnV), or multimodal (AnVn) noise. Acoustic and visual noises were matched in physical signal-to-noise ratio. Eyetracking monitored participants' gaze to different parts of a talker's face during SIN perception. RESULTS: As expected, behavioral performance for clean sentence recognition was better for A-only and AV compared to V-only speech. Similarly, with noise in the auditory channel (AnV and AnVn speech), performance was aided by the addition of visual cues of the talker regardless of whether the visual channel contained noise, confirming a multimodal benefit to SIN recognition. The addition of visual noise (AVn) obscuring the talker's face had little effect on speech recognition by itself. Listeners' eye gaze fixations were biased toward the eyes (decreased at the mouth) whenever the auditory channel was compromised. Fixating on the eyes was negatively associated with SIN recognition performance. Eye gazes on the mouth versus eyes of the face also depended on the gender of the talker. CONCLUSIONS: Collectively, results suggest listeners (1) depend heavily on the auditory over visual channel when seeing and hearing speech and (2) alter their visual strategy from viewing the mouth to viewing the eyes of a talker with signal degradations, which negatively affects speech perception.

Myelodysplastic neoplasm-associated U2AF1 mutations induce host defense defects by compromising neutrophil chemotaxis.

Myelodysplastic neoplasm (MDS) is a hematopoietic stem cell disorder that may evolve into acute myeloid leukemia. Fatal infection is among the most common cause of death in MDS patients, likely due to myeloid cell cytopenia and dysfunction in these patients. Mutations in genes that encode components of the spliceosome represent the most common class of somatically acquired mutations in MDS patients. To determine the molecular underpinnings of the host defense defects in MDS patients, we investigated the MDS-associated spliceosome mutation U2AF1-S34F using a transgenic mouse model that expresses this mutant gene. We found that U2AF1-S34F causes a profound host defense defect in these mice, likely by inducing a significant neutrophil chemotaxis defect. Studies in human neutrophils suggest that this effect of U2AF1-S34F likely extends to MDS patients as well. RNA-seq analysis suggests that the expression of multiple genes that mediate cell migration are affected by this spliceosome mutation and therefore are likely drivers of this neutrophil dysfunction.

Musical experience partially counteracts temporal speech processing deficits in putative mild cognitive impairment.

Mild cognitive impairment (MCI) commonly results in more rapid cognitive and behavioral declines than typical aging. Individuals with MCI can exhibit impaired receptive speech abilities that may reflect neurophysiological changes in auditory-sensory processing prior to usual cognitive deficits. Benefits from current interventions targeting communication difficulties in MCI are limited. Yet, neuroplasticity associated with musical experience has been implicated in improving neural representations of speech and offsetting age-related declines in perception. Here, we asked whether these experience-dependent effects of musical experience might extend to aberrant aging and offer some degree of cognitive protection against MCI. During a vowel categorization task, we recorded single-channel electroencephalograms (EEGs) in older adults with putative MCI to evaluate speech encoding across subcortical and cortical levels of the auditory system. Critically, listeners varied in their duration of formal musical experience (0-21 years). Musical experience sharpened temporal precision in auditory cortical responses, suggesting that musical experience produces more efficient processing of acoustic features by counteracting age-related neural delays. Additionally, robustness of brainstem responses predicted the severity of cognitive decline, suggesting that early speech representations are sensitive to preclinical stages of cognitive impairment. Our results extend prior studies by demonstrating positive benefits of musical experience in older adults with emergent cognitive impairments.

Bilateral Tubal Ectopic Pregnancy Following Clomiphene Administration: A Case Report.

A bilateral tubal ectopic pregnancy is the rarest form of extrauterine pregnancy and is extremely difficult to diagnose due to an initial presentation that is nearly indistinguishable from unilateral tubal ectopic pregnancy. We report a case of a 27-year-old primigravida woman who presented to our clinic with mild cramping and vaginal bleeding following the administration of clomiphene. Ultrasound confirmed the presence of a left-sided ectopic pregnancy. The patient underwent laparoscopy and was found to have a mass in the contralateral fallopian tube. Histologic evaluation of the specimens from both fallopian tubes confirmed the presence of a simultaneous bilateral tubal ectopic pregnancy. While no current guidelines exist for the management of bilateral ectopic pregnancies, we stress the importance of direct visualization of both fallopian tubes during laparoscopy for any suspected ectopic pregnancy.

Defining the Role of Attention in Hierarchical Auditory Processing.

Communication in noise is a complex process requiring efficient neural encoding throughout the entire auditory pathway as well as contributions from higher-order cognitive processes (i.e., attention) to extract speech cues for perception. Thus, identifying effective clinical interventions for individuals with speech-in-noise deficits relies on the disentanglement of bottom-up (sensory) and top-down (cognitive) factors to appropriately determine the area of deficit; yet, how attention may interact with early encoding of sensory inputs remains unclear. For decades, attentional theorists have attempted to address this question with cleverly designed behavioral studies, but the neural processes and interactions underlying attention's role in speech perception remain unresolved. While anatomical and electrophysiological studies have investigated the neurological structures contributing to attentional processes and revealed relevant brain-behavior relationships, recent electrophysiological techniques (i.e., simultaneous recording of brainstem and cortical responses) may provide novel insight regarding the relationship between early sensory processing and top-down attentional influences. In this article, we review relevant theories that guide our present understanding of attentional processes, discuss current electrophysiological evidence of attentional involvement in auditory processing across subcortical and cortical levels, and propose areas for future study that will inform the development of more targeted and effective clinical interventions for individuals with speech-in-noise deficits.

Auditory-frontal Channeling in α and ß Bands is Altered by Age-related Hearing Loss and Relates to Speech Perception in Noise.

Difficulty understanding speech-in-noise (SIN) is a pervasive problem faced by older adults particularly those with hearing loss. Previous studies have identified structural and functional changes in the brain that contribute to older adults' speech perception difficulties. Yet, many of these studies use neuroimaging techniques that evaluate only gross activation in isolated brain regions. Neural oscillations may provide further insight into the processes underlying SIN perception as well as the interaction between auditory cortex and prefrontal linguistic brain regions that mediate complex behaviors. We examined frequency-specific neural oscillations and functional connectivity of the EEG in older adults with and without hearing loss during an active SIN perception task. Brain-behavior correlations revealed listeners who were more resistant to the detrimental effects of noise also demonstrated greater modulation of α phase coherence between clean and noise-degraded speech, suggesting α desynchronization reflects release from inhibition and more flexible allocation of neural resources. Additionally, we found top-down ß connectivity between prefrontal and auditory cortices strengthened with poorer hearing thresholds despite minimal behavioral differences. This is consistent with the proposal that linguistic brain areas may be recruited to compensate for impoverished auditory inputs through increased top-down predictions to assist SIN perception. Overall, these results emphasize the importance of top-down signaling in low-frequency brain rhythms that help compensate for hearing-related declines and facilitate efficient SIN processing.

Afferent-efferent connectivity between auditory brainstem and cortex accounts for poorer speech-in-noise comprehension in older adults.

Speech-in-noise (SIN) comprehension deficits in older adults have been linked to changes in both subcortical and cortical auditory evoked responses. However, older adults' difficulty understanding SIN may also be related to an imbalance in signal transmission (i.e., functional connectivity) between brainstem and auditory cortices. By modeling high-density scalp recordings of speech-evoked responses with sources in brainstem (BS) and bilateral primary auditory cortices (PAC), we show that beyond attenuating neural activity, hearing loss in older adults compromises the transmission of speech information between subcortical and early cortical hubs of the speech network. We found that the strength of afferent BS→PAC neural signaling (but not the reverse efferent flow; PAC→BS) varied with mild declines in hearing acuity and this "bottom-up" functional connectivity robustly predicted older adults' performance in a SIN identification task. Connectivity was also a better predictor of SIN processing than unitary subcortical or cortical responses alone. Our neuroimaging findings suggest that in older adults (i) mild hearing loss differentially reduces neural output at several stages of auditory processing (PAC > BS), (ii) subcortical-cortical connectivity is more sensitive to peripheral hearing loss than top-down (cortical-subcortical) control, and (iii) reduced functional connectivity in afferent auditory pathways plays a significant role in SIN comprehension problems.