Relating monaural and binaural measures of modulation sensitivity in listeners with and without hearing loss.

Listeners are sensitive to interaural time differences carried in the envelope of high-frequency sounds (ITDENV), but the salience of this cue depends on certain properties of the envelope and, in particular, on the presence/depth of amplitude modulation (AM) in the envelope. This study tested the hypothesis that individuals with sensorineural hearing loss, who show enhanced sensitivity to AM under certain conditions, would also show superior ITDENV sensitivity under those conditions. The second hypothesis was that variations in ITDENV sensitivity across individuals can be related to variations in sensitivity to AM. To enable a direct comparison, a standard adaptive AM detection task was used along with a modified version of it designed to measure ITDENV sensitivity. The stimulus was a 4-kHz tone modulated at rates of 32, 64, or 128 Hz and presented at a 30 dB sensation level. Both tasks were attempted by 16 listeners with normal hearing and 16 listeners with hearing loss. Consistent with the hypotheses, AM and ITDENV thresholds were correlated and tended to be better in listeners with hearing loss. A control experiment emphasized that absolute level may be a consideration when interpreting the group effects.

De novo genome assembly of a Geomyid rodent, Botta's pocket gopher (Thomomys bottae bottae).

Botta's pocket gopher (Thomomys bottae) is a common and widespread subterranean rodent of the North American west. The species has been of long interest to evolutionary biologists due to the phenotypic diversity across its range and unusual levels of variation in chromosome number and composition. Here, we present a high-quality reference genome from a male T. b. bottae individual captured in the San Francisco Bay Area. The assembly is comprised of 2,792 scaffolds, with a scaffold N50 value of 23.6 Mb and a BUSCO score of 91.0%. This genome helps fill a significant taxonomic sampling gap in rodent genome resources. With this reference genome, we envision new opportunities to investigate questions regarding the genomics of adaptation to the belowground niche. Further, we can begin to explore the impact of associated life history traits, such as limited dispersal and low population connectivity, on intraspecific genetic and phenotypic variation, genome evolution, speciation, and phylogenetic relationships across the Geomyoidea.

Dual Atypical Antipsychotics in Treatment-Resistant Schizophrenia: A Correctional Case Report and Review of Literature.

Treatment-resistant schizophrenia (TRS) is a challenging condition to treat for the correctional psychiatrist. Guidelines from the American Psychiatric Association indicate that the first-line pharmacotherapy for TRS is the use of the atypical antipsychotic clozapine. The use of clozapine is unique in that it requires patient adherence with weekly blood draws as a prophylactic measure against agranulocytosis and leukopenia. In the correctional setting, patients with severe and persistent schizophrenia are frequently nonadherent due to lack of insight and anemic access to health care resources, specifically as these pertain to clozapine. Therefore, an alternative treatment option would be a welcome solution for this demographic. Our literature review demonstrates a limited number of studies documenting the successful use of clozapine alternatives or combination antipsychotic therapy for treatment of TRS. In this article, we present a putative case where we believe that a combination regimen of paliperidone palmitate, oral aripiprazole, and escitalopram led to a notable mitigation of both positive and negative symptoms of psychosis in the case of an incarcerated patient with TRS, as well as an improvement in functional stability, which was conducive to housing in a less restrictive setting. A brief review of the published literature follows the report.

Inhibitory tagging both speeds and strengthens saccade target selection in the superior colliculus during visual search.

It has been suggested that, during difficult visual search tasks involving time pressure and multiple saccades, inhibitory tagging helps to facilitate efficient saccade target selection by reducing responses to objects in the scene once they have been searched and rejected. The superior colliculus (SC) is a midbrain structure involved in target selection, and recent findings suggest an influence of inhibitory tagging on SC activity. Precisely how, and by how much, inhibitory tagging influences target selection by SC neurons, however, is unclear. The purpose of this study, therefore, was to characterize and quantify the influence of inhibitory tagging on target selection in the SC. Rhesus monkeys performed a visual search task involving time pressure and multiple saccades. Early in the fixation period between saccades in the context of this task, a subset of SC neurons reliably discriminated the stimulus selected as the next saccade goal, consistent with a role in target selection. Discrimination occurred earlier and was more robust, however, when unselected stimuli in the search array had been previously fixated on the same trial. This indicates that inhibitory tagging both speeds and strengthens saccade target selection in the SC during multisaccade search. The results provide constraints on models of target selection based on SC activity.NEW & NOTEWORTHY An important aspect of efficient behavior during difficult, time-limited visual search tasks is the efficient selection of sequential saccade targets. Inhibitory tagging, i.e., a reduction of neural activity associated with previously fixated objects, may help to facilitate such efficient selection by modulating the selection process in the superior colliculus (SC). In this study, we characterized and quantified this modulation and found that, indeed, inhibitory tagging both speeds and strengthens target selection in the SC.

Inhibitory tagging both speeds and strengthens saccade target selection in the superior colliculus during visual search.

It has been suggested that, during difficult visual search tasks involving time pressure and multiple saccades, inhibitory tagging helps to facilitate efficient saccade target selection by reducing responses to objects in the scene once they have been searched and rejected. The superior colliculus (SC) is a midbrain structure involved in target selection, and recent findings suggest an influence of inhibitory tagging on SC activity. Precisely how, and by how much, inhibitory tagging influences target selection by SC neurons, however, is unclear. The purpose of this study, therefore, was to characterize and quantify the influence of inhibitory tagging on target selection in the SC. Rhesus monkeys performed a visual search task involving time pressure and multiple saccades. Early in the fixation period between saccades, a subset of SC neurons reliably discriminated the stimulus selected as the next saccade goal, consistent with a role in target selection. Discrimination occurred earlier and was more robust, however, when unselected stimuli in the search array had been previously fixated on the same trial. This indicates that inhibitory tagging both speeds and strengthens saccade target selection in the SC during multisaccade search. The results provide constraints on models of target selection based on SC activity.

Pronounced Regional Variation in Esketamine and Ketamine Prescribing to US Medicaid Patients.

Ketamine and esketamine are efficacious for treatment-resistant depression. Unlike other antidepressants, ketamine lacks a therapeutic delay and decreases the risk for suicide. This cross-sectional study geographically characterized ketamine and esketamine prescribing to United States (US) Medicaid patients. Ketamine and esketamine prescription rates and spending per state were obtained. Between 2009 and 2020, ketamine prescribing rates peaked in 2013 followed by a general decline. For ketamine and esketamine in 2019, Montana (967/million enrollees) and Indiana (425) showed significantly higher prescription rates, respectively, relative to the national average. A total of 21 states prescribed neither ketamine nor esketamine in 2019. There was a 121.3% increase in esketamine prescriptions from 2019 to 2020. North Dakota (1,423) and North Carolina (1,094) were significantly elevated relative to the average state for esketamine in 2020. Ten states prescribed neither ketamine nor esketamine in 2020. Medicaid programs in 2020 spent 72.7-fold more for esketamine ($25.3 million) than on ketamine (0.3 million). Despite the effectiveness of ketamine and esketamine for treatment-resistant depression and anti-suicidal properties, their use among Medicaid patients was limited and highly variable in many areas of the US. Further research to better understand the origins of this state-level variation is needed.

Individual differences in speech-on-speech masking are correlated with cognitive and visual task performance.

Individual differences in spatial tuning for masked target speech identification were determined using maskers that varied in type and proximity to the target source. The maskers were chosen to produce three strengths of informational masking (IM): high [same-gender, speech-on-speech (SOS) masking], intermediate (the same masker speech time-reversed), and low (speech-shaped, speech-envelope-modulated noise). Typical for this task, individual differences increased as IM increased, while overall performance decreased. To determine the extent to which auditory performance might generalize to another sensory modality, a comparison visual task was also implemented. Visual search time was measured for identifying a cued object among "clouds" of distractors that were varied symmetrically in proximity to the target. The visual maskers also were chosen to produce three strengths of an analog of IM based on feature similarities between the target and maskers. Significant correlations were found for overall auditory and visual task performance, and both of these measures were correlated with an index of general cognitive reasoning. Overall, the findings provide qualified support for the proposition that the ability of an individual to solve IM-dominated tasks depends on cognitive mechanisms that operate in common across sensory modalities.

Inhibitory tagging in the superior colliculus during visual search.

Inhibitory tagging is an important feature of many models of saccade target selection, in particular those that are based on the notion of a neural priority map. The superior colliculus (SC) has been suggested as a potential site of such a map, yet it is unknown whether inhibitory tagging is represented in the SC during visual search. In this study, we tested the hypothesis that SC neurons represent inhibitory tagging during search, as might be expected if they contribute to a priority map. To do so, we recorded the activity of SC neurons in a multisaccade visual-search task. On each trial, a single reward-bearing target was embedded in an array of physically identical, potentially reward-bearing targets and physically distinct, non-reward-bearing distractors. The task was to fixate the reward-bearing target. We found that, in the context of this task, the activity of many SC neurons was greater when their response field stimulus was a target than when it was a distractor and was reduced when it had been previously fixated relative to when it had not. Moreover, we found that the previous-fixation-related reduction of activity was larger for targets than for distractors and decreased with increasing time (or number of saccades) since fixation. Taken together, the results suggest that fixated stimuli are transiently inhibited in the SC during search, consistent with the notion that inhibitory tagging plays an important role in visual search and that SC neurons represent this inhibition as part of a priority map used for saccade target selection.NEW & NOTEWORTHY Searching a cluttered scene for an object of interest is a ubiquitous task in everyday life, which we often perform relatively quickly and efficiently. It has been suggested that to achieve such speed and efficiency an inhibitory-tagging mechanism inhibits saccades to objects in the scene once they have been searched and rejected. Here, we demonstrate that the superior colliculus represents this type of inhibition during search, consistent with its role in saccade target selection.

Cues to reduce modulation informational masking.

The detectability of target amplitude modulation (AM) can be reduced by masker AM in the same carrier-frequency region. It can be reduced even further, however, if the masker-AM rate is uncertain [Conroy and Kidd, J. Acoust. Soc. Am. 149, 3665-3673 (2021)]. This study examined the effectiveness of contextual cues in reducing this latter, uncertainty-related effect (modulation informational masking). Observers were tasked with detecting fixed-rate target sinusoidal amplitude modulation (SAM) in the presence of masker SAM applied simultaneously to the same broadband-noise carrier. A single-interval, two-alternative forced-choice detection procedure was used to measure sensitivity for the target SAM; masker-AM-rate uncertainty was created by randomly selecting the AM rate of the masker SAM on each trial. Relative to an uncued condition, a pretrial cue to the masker SAM significantly improved sensitivity for the target SAM; a cue to the target SAM, however, did not. The delay between the cue-interval offset and trial-interval onset did not affect the size of the masker-cue benefit, suggesting that adaptation of the masker SAM was not responsible. A simple model of within-AM-channel masking captured important trends in the psychophysical data, suggesting that reduced masker-AM-rate uncertainty may have played a relatively minor role in the masker-cue benefit.

Forward masking of spectrotemporal modulation detection.

Recent work has suggested that there may be specialized mechanisms in the auditory system for coding spectrotemporal modulations (STMs), tuned to different combinations of spectral modulation frequency, temporal modulation frequency, and STM sweep direction. The current study sought evidence of such mechanisms using a psychophysical forward masking paradigm. The detectability of a target comprising upward sweeping STMs was measured following the presentation of modulated maskers applied to the same carrier. Four maskers were tested, which had either (1) the same spectral modulation frequency as the target but a flat temporal envelope, (2) the same temporal modulation frequency as the target but a flat spectral envelope, (3) the same spectral and temporal modulation frequencies as the target but the opposite sweep direction (downward sweeping STMs), or (4) the same spectral and temporal modulation frequencies as the target and the same sweep direction (upward sweeping STMs). Forward masking was greatest for the masker fully matched to the target (4), intermediate for the masker with the opposite sweep direction (3), and negligible for the other two (1, 2). These findings are consistent with the suggestion that the detectability of the target was mediated by an STM-specific coding mechanism with sweep-direction selectivity.

The Effects of Uncertainty in Level on Speech-on-Speech Masking.

Identification of speech from a "target" talker was measured in a speech-on-speech masking task with two simultaneous "masker" talkers. The overall level of each talker was either fixed or randomized throughout each stimulus presentation to investigate the effectiveness of level as a cue for segregating competing talkers and attending to the target. Experimental manipulations included varying the level difference between talkers and imposing three types of target level uncertainty: 1) fixed target level across trials, 2) random target level across trials, or 3) random target levels on a word-by-word basis within a trial. When the target level was predictable performance was better than corresponding conditions when the target level was uncertain. Masker confusions were consistent with a high degree of informational masking (IM). Furthermore, evidence was found for "tuning" in level and a level "release" from IM. These findings suggest that conforming to listener expectation about relative level, in addition to cues signaling talker identity, facilitates segregation of, and maintaining focus of attention on, a specific talker in multiple-talker communication situations.

Informational masking in the modulation domain.

Uncertainty regarding the frequency spectrum of a masker can have an adverse effect on the ability to focus selective attention on a target frequency channel, yielding informational masking (IM). This study sought to determine if uncertainty regarding the modulation spectrum of a masker can have an analogous adverse effect on the ability to focus selective attention on a target modulation channel, yielding IM in the modulation domain, or "modulation IM." A single-interval, two-alternative forced-choice (yes-no) procedure was used. The task was to detect 32-Hz target sinusoidal amplitude modulation (SAM) imposed on a broadband-noise carrier in the presence of masker SAM imposed on the same carrier. Six maskers, spanning the range from 8 to 128 Hz in half-octave steps, were tested, excluding those that fell within a two-octave protected zone surrounding the target. Psychometric functions (d'-vs-target modulation depth) were measured for each masker under two conditions: a fixed (low-uncertainty/low-IM) condition, in which the masker was the same on all trials within a block, and a random (high-uncertainty/high-IM) condition, in which it varied randomly from presentation-to-presentation. Thresholds and slopes extracted from the psychometric functions differed markedly between the conditions. These results are consistent with the idea that IM occurs in the modulation domain.

Uncertainty about amplitude eliminates negative masking in a pure-tone amplitude discrimination experiment.

The role of uncertainty and its reduction in producing the "negative masking" of amplitude increments that is often observed in pure-tone amplitude discrimination experiments using circathreshold pedestals was investigated. It was found that negative masking is eliminated by uncertainty induced by roving the pedestal level across trials. On the basis of this finding, as well as those from a previous study, it is argued that, consistent with a longstanding theory of negative masking based on the notion of "intrinsic uncertainty," negative masking requires near-optimal stimulus conditions, under which uncertainty about increment parameters is more or less absent.

The importance of processing resolution in "ideal time-frequency segregation" of masked speech and the implications for predicting speech intelligibility.

Ideal time-frequency segregation (ITFS) is a signal processing technique that may be used to estimate the energetic and informational components of speech-on-speech masking. A core assumption of ITFS is that it roughly emulates the effects of energetic masking (EM) in a speech mixture. Thus, when speech identification thresholds are measured for ITFS-processed stimuli and compared to thresholds for unprocessed stimuli, the difference can be attributed to informational masking (IM). Interpreting this difference as a direct metric of IM, however, is complicated by the fine time-frequency (T-F) resolution typically used during ITFS, which may yield target "glimpses" that are too narrow/brief to be resolved by the ear in the mixture. Estimates of IM, therefore, may be inflated because the full effects of EM are not accounted for. Here, T-F resolution was varied during ITFS to determine if/how estimates of IM depend on processing resolution. Speech identification thresholds were measured for speech and noise maskers after ITFS. Reduced frequency resolution yielded poorer thresholds for both masker types. Reduced temporal resolution did so for noise maskers only. Results suggest that processing resolution strongly influences estimates of IM and implies that current approaches to predicting masked speech intelligibility should be modified to account for IM.

Gut microbial diversity across a contact zone for California voles: Implications for lineage divergence of hosts and mitonuclear mismatch in the assembly of the mammalian gut microbiome.

Gut microbial diversity is thought to reflect the co-evolution of microbes and their hosts as well as current host-specific attributes such as genetic background and environmental setting. To explore interactions among these parameters, we characterized variation in gut microbiome composition of California voles (Microtus californicus) across a contact zone between two recently diverged lineages of this species. Because this contact zone contains individuals with mismatched mitochondrial-nuclear genomes (cybrids), it provides an important opportunity to explore how different components of the genotype contribute to gut microbial diversity. Analyses of bacterial 16S rRNA sequences and joint species distribution modelling revealed that host genotypes and genetic differentiation among host populations together explained more than 50% of microbial community variation across our sampling transect. The ranked importance (most to least) of factors contributing to gut microbial diversity in our study populations were: genome-wide population differentiation, local environmental conditions, and host genotypes. However, differences in microbial communities among vole populations (ß-diversity) did not follow patterns of lineage divergence (i.e., phylosymbiosis). Instead, among-population variation was best explained by the spatial distribution of hosts, as expected if the environment is a primary source of gut microbial diversity (i.e., dispersal limitation hypothesis). Across the contact zone, several bacterial taxa differed in relative abundance between the two parental lineages as well as among individuals with mismatched mitochondrial and nuclear genomes. Thus, genetic divergence among host lineages and mitonuclear genomic mismatches may also contribute to microbial diversity by altering interactions between host genomes and gut microbiota (i.e., hologenome speciation hypothesis).

Can background noise increase the informational masking in a speech mixture?

This study tested the hypothesis that adding noise to a speech mixture may cause both energetic masking by obscuring parts of the target message and informational masking by impeding the segregation of competing voices. The stimulus was the combination of two talkers-one target and one masker-presented either in quiet or in noise. Target intelligibility was measured in this mixture and for conditions in which the speech was "glimpsed" in order to quantify the energetic masking present. The results suggested that the addition of background noise exacerbated informational masking, primarily by increasing the sparseness of the speech.

Informational masking of negative masking.

Negative masking (NM) is a ubiquitous finding in near-"threshold" psychophysics in which the detectability of a near-threshold signal improves when added to a copy of itself, i.e., a pedestal or masker. One interpretation of NM suggests that the pedestal acts as an informative cue, thereby reducing uncertainty and improving performance relative to detection in its absence. The purpose of this study was to test this hypothesis. Intensity discrimination thresholds were measured for 100-ms, 1000-Hz near-threshold tones. In the reference condition, thresholds were measured in quiet (no masker other than the pedestal). In comparison conditions, thresholds were measured in the presence of one of two additional maskers: a notched-noise masker or a random-frequency multitone masker. The additional maskers were intended to cause different amounts of uncertainty and, in turn, to differentially influence NM. The results were generally consistent with an uncertainty-based interpretation of NM: NM was found both in quiet and in notched-noise, yet it was eliminated by the multitone masker. A competing interpretation of NM based on nonlinear transduction does not account for all of the results. Profile analysis may have been a factor in performance and this suggests that NM may be attributable to, or influenced by, multiple mechanisms.

Mito-nuclear discordance across a recent contact zone for California voles.

To examine the processes that maintain genetic diversity among closely related taxa, we investigated the dynamics of introgression across a contact zone between two lineages of California voles (Microtus californicus). We tested the prediction that introgression of nuclear loci would be greater than that for mitochondrial loci, assuming ongoing gene flow across the contact zone. We also predicted that genomic markers would show a mosaic pattern of differentiation across this zone, consistent with genomes that are semi-permeable. Using mitochondrial cytochrome b sequences and genome-wide loci developed via ddRAD-seq, we analyzed genetic variation for 10 vole populations distributed along the central California coast; this transect included populations from within the distributions of both parental lineages as well as the putative contact zone. Our analyses revealed that (1) the two lineages examined are relatively young, having diverged ca. 8.5-54 kya, (2) voles from the contact zone in Santa Barbara County did not include F1 or early generation backcrossed individuals, and (3) there appeared to be little to no recurrent gene flow across the contact zone. Introgression patterns for mitochondrial and nuclear markers were not concordant; only mitochondrial markers revealed evidence of introgression, putatively due to historical hybridization. These differences in genetic signatures are intriguing given that the contact zone occurs in a region of continuous vole habitat, with no evidence of past or present physical barriers. Future studies that examine specific isolating mechanisms, such as microhabitat use and mate choice, will facilitate our understanding of how genetic boundaries are maintained in this system.

Apical Elongation of Molar Teeth in Captive Microtus Voles.

Molar apical elongation (MAE) was the leading cause for euthanasia or death in a captive breeding colony of endangered Amargosa voles ( Microtus californicus scirpensis). Clinical signs included ocular discharge, abnormal mastication, dyspnea, abnormal mentation, weight loss, and death. Although the severity varied, all molars in all quadrants were affected. When severe, the overgrown molar reserve crown and apex protruded into the nasal meatuses, the orbit, the calvarial vault and through the ventral margin of the mandible. Overall prevalence in the colony was 63% (92/146 voles) and increased to 77% in aged voles (>1 year). Mean age of onset was 5.3 months (1.7-11.2 months). Progression to extreme severity occurred over 1 to 3 months. Mean survival was 10.9 months (7.1-21.7 months). Histologically, the lesion was characterized by odontogenic hyperplasia and dysplasia. MAE was also documented in museum specimens of 2 other M. californicus subspecies ( M. californicus californicus, M. californicus vallicola) and 3 other Microtus species ( M. montanus, M. pennsylvanicus, M. socialis). In the M. californicus californicus collection, overall prevalence was 35.1% (129/368 skulls) and increased to 77.3% in aged voles (>1 year). A probable genetic influence was identified in the museum collection of M. californicus californicus. The etiopathogenesis of MAE is likely multifactorial, due to (1) inherent continuous odontogenic proliferation, (2) inadequate occlusal attrition, and (3) possible heritable disease susceptibility. In captivity, dietary or other management of occlusal attrition to prevent or delay MAE is a fundamental concern.