Spatial hearing evolved independently in mammals and birds, and is thought to adapt to altered developmental input in different ways. We found, however, that ferrets possess multiple forms of plasticity that are expressed according to which spatial cues are available, suggesting that the basis for adaptation may be similar across species. Our results also provide insight into the way sound source location is represented by populations of cortical neurons.
The precise encoding of temporal features of auditory stimuli by the mammalian auditory system is critical to the perception of biologically important sounds, including vocalizations, speech, and music. In this study, auditory gap-detection behavior was evaluated in adult pigmented ferrets (Mustelid putorius furo) using bandpassed stimuli designed to widely sample the ferret’s behavioral and physiological audiogram. Animals were tested under positive operant conditioning, with psychometric functions constructed in response to gap-in-noise lengths ranging from 3 to 270 ms. Using a modified version of this gap-detection task, with the same stimulus frequency parameters, we also tested a cohort of normal-hearing human subjects. Gap-detection thresholds were computed from psychometric curves transformed according to signal detection theory, revealing that for both ferrets and humans, detection sensitivity was worse for silent gaps embedded within low-frequency noise compared with high-frequency or broadband stimuli. Additional psychometric function analysis of ferret behavior indicated effects of stimulus spectral content on aspects of behavioral performance related to decision-making processes, with animals displaying improved sensitivity for broadband gap-in-noise detection. Reaction times derived from unconditioned head-orienting data and the time from stimulus onset to reward spout activation varied with the stimulus frequency content and gap length, as well as the approach-to-target choice and reward location. The present study represents a comprehensive evaluation of gap-detection behavior in ferrets, while similarities in performance with our human subjects confirm the use of the ferret as an appropriate model of temporal processing.
ferret; human; behavior; temporal processing; auditory gap detection
How an animal moves through its environment directly impacts its survival, reproduction, and thus biological fitness. A basic measure describing how an individual (or group) travels through its environment is Day Path Length (DPL), i.e., the distance travelled in a 24-hour period. Here, we investigate the ecological determinants of baboon (Papio spp.) troop DPL and movements at local and continental scales.
At the continental scale we explore the ecological determinants of annual mean DPL for 47 baboon troops across 23 different populations, updating a classic study by Dunbar (Behav Ecol Sociobiol 31: 35-49, 1992). We find that variation in baboon DPLs is predicted by ecological dissimilarity across the genus range. Troops that experience higher average monthly rainfall and anthropogenic influences have significantly shorter DPL, whilst troops that live in areas with higher average annual temperatures have significantly longer DPL. We then explore DPLs and movement characteristics (the speed and distribution of turning angles) for yellow baboons (Papio cynocephalus) at a local scale, in the Issa Valley of western Tanzania. We show that our continental-scale model is a good predictor of DPL in Issa baboons, and that troops move significantly slower, and over shorter distances, on warmer days. We do not find any effect of season or the abundance of fruit resources on the movement characteristics or DPL of Issa baboons, but find that baboons moved less during periods of high fruit availability.
Overall, this study emphasises the ability of baboons to adapt their ranging behaviour to a range of ecological conditions and highlights how investigations of movement patterns at different spatial scales can provide a more thorough understanding of the ecological determinants of movement.
Electronic supplementary material
The online version of this article (doi:10.1186/s40462-015-0040-y) contains supplementary material, which is available to authorized users.
Day path length; Baboon; Papio cynocephalus; Season; Space-use; Ranging; Modelling; Speed; Turning angle; Human-modified habitat; Movement characteristics; Comparative analysis
A group of multidisciplinary sonologists conduct weekly Intensive Care Unit (ICU) rounds consisting of ultrasound examinations on select patients recommended by the critical care staff. This image was acquired on a 51-year-old male in the ICU with known valve vegetations, and a pleural adhesion was incidentally discovered on ultrasound.
Pleural effusion; thoracostomy; ultrasound
Valuable insights into the role of experience in shaping perception can be obtained by studying the effects of blindness or other forms of sensory deprivation on the intact senses. Blind individuals are particularly dependent on their hearing and there is extensive evidence that they can develop superior auditory skills, either as a result of plasticity within the auditory system or through the recruitment of functionally relevant occipital cortical areas that lack their normal visual inputs. Because spatial processing normally relies on close interactions between vision and hearing, much of the research in this area has focused on the effects of blindness on auditory localization. Although enhanced auditory skills have been reported in many studies, some aspects of spatial hearing are impaired in the absence of vision. In this case, the effects of crossmodal plasticity may reflect a balance between adaptive changes that compensate for blindness and the role vision normally plays, particularly during development, in calibrating the brain’s representation of auditory space.
Blindness; Auditory localization; Cortex; Experience-dependent plasticity; Functional reorganization
A recent study shows that expectation about the timing of behaviorally-relevant sounds enhances the responses of neurons in the primary auditory cortex and improves the accuracy and speed with which animals respond to those sounds.
The recent discovery of combination-sensitive neurons in the primary auditory cortex of awake marmosets may reconcile previous, apparently contradictory, findings that cortical neurons produce strong, sustained responses, but also represent stimuli sparsely.
A new study finds that neurons in the ferret frontal cortex typically respond to sound only during trained auditory tasks and that these neurons depict the task-related meaning rather than the acoustical properties of stimuli.
Two recent studies have described how the coupling of excitatory and inhibitory inputs to neurons in the auditory cortex changes during development. This process is driven by experience and, once complete, may limit the plasticity of the cortex in later life.
A recent study provides intriguing insights into how we recognize the sound of everyday objects from the statistical properties of the textures they produce.
Mutations in the gene encoding profilin 1 (PFN1) have recently been shown to cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. We sequenced the PFN1 gene in a cohort of ALS patients (n = 485) and detected 2 novel variants (A20T and Q139L), as well as 4 cases with the previously identified E117G rare variant (∼ 1.2%). A case-control meta-analysis of all published E117G ALS+/− frontotemporal dementia cases including those identified in this report was significant p = 0.001, odds ratio = 3.26 (95% confidence interval, 1.6–6.7), demonstrating this variant to be a susceptibility allele. Postmortem tissue from available patients displayed classic TAR DNA-binding protein 43 pathology. In both transient transfections and in fibroblasts from a patient with the A20T change, we showed that this novel PFN1 mutation causes protein aggregation and the formation of insoluble high molecular weight species which is a hallmark of ALS pathology. Our findings show that PFN1 is a rare cause of ALS and adds further weight to the underlying genetic heterogeneity of this disease.
Amyotrophic lateral sclerosis; Profilin 1; TDP-43 proteinopathy
Multisensory integration was once thought to be the domain of brain areas high in the cortical hierarchy, with early sensory cortical fields devoted to unisensory processing of inputs from their given set of sensory receptors. More recently, a wealth of evidence documenting visual and somatosensory responses in auditory cortex, even as early as the primary fields, has changed this view of cortical processing. These multisensory inputs may serve to enhance responses to sounds that are accompanied by other sensory cues, effectively making them easier to hear, but may also act more selectively to shape the receptive field properties of auditory cortical neurons to the location or identity of these events. We discuss the new, converging evidence that multiplexing of neural signals may play a key role in informatively encoding and integrating signals in auditory cortex across multiple sensory modalities. We highlight some of the many open research questions that exist about the neural mechanisms that give rise to multisensory integration in auditory cortex, which should be addressed in future experimental and theoretical studies.
Multisensory; Auditory Cortex; Perception; Multiplex; Information; Neural code; Visual; Somatosensory
Neurons responsive to visual stimulation have now been described in the auditory cortex of various species, but their functions are largely unknown. Here we investigate the auditory and visual spatial sensitivity of neurons recorded in 5 different primary and non-primary auditory cortical areas of the ferret. We quantified the spatial tuning of neurons by measuring the responses to stimuli presented across a range of azimuthal positions and calculating the mutual information (MI) between the neural responses and the location of the stimuli that elicited them. MI estimates of spatial tuning were calculated for unisensory visual, unisensory auditory and for spatially and temporally coincident auditory-visual stimulation. The majority of visually responsive units conveyed significant information about light-source location, whereas, over a corresponding region of space, acoustically responsive units generally transmitted less information about sound-source location. Spatial sensitivity for visual, auditory and bisensory stimulation was highest in the anterior dorsal field, the auditory area previously shown to be innervated by a region of extrastriate visual cortex thought to be concerned primarily with spatial processing, whereas the posterior pseudosylvian field and posterior suprasylvian field, whose principal visual input arises from cortical areas that appear to be part of the ‘what’ processing stream, conveyed less information about stimulus location. In some neurons, pairing visual and auditory stimuli led to an increase in the spatial information available relative to the most effective unisensory stimulus, whereas, in a smaller subpopulation, combined stimulation decreased the spatial MI. These data suggest that visual inputs to auditory cortex can enhance spatial processing in the presence of multisensory cues and could therefore potentially underlie visual influences on auditory localization.
Multisensory; Ferret; Single-unit recording; Virtual acoustic space; Mutual information; Sound localization
Amyotrophic lateral sclerosis (ALS) is a primary progressive neurodegenerative disease characterised by neuronal loss of lower motor neurons (in the spinal cord and brainstem) and/or upper motor neurons (in the motor cortex) and subsequent denervation atrophy of skeletal muscle.
A comprehensive examination of muscle pathology from a cohort of clinically confirmed ALS patients, including an investigation of inflammation, complement activation, and deposition of abnormal proteins in order to compare them with findings from an age-matched, control group.
Material and methods
31 muscle biopsies from clinically confirmed ALS patients and 20 normal controls underwent a comprehensive protocol of histochemical and immunohistochemical stains, including HLA-ABC, C5b-9, p62, and TDP-43.
Neurogenic changes were confirmed in 30/31 ALS cases. In one case, no neurogenic changes could be detected. Muscle fibre necrosis was seen in 5/31 cases and chronic mononuclear inflammatory cell infiltration in 5/31 (2 of them overlapped with those showing muscle necrosis). In four biopsies there was an increase in the proportion of cytochrome oxidase (COX) negative fibres (2-3%). p62 faintly stained cytoplasmic bodies in eight cases and none were immunoreactive to TDP-43.
This large series of muscle biopsies from patients with ALS demonstrates neurogenic atrophy is a nearly uniform finding and that mild mitochondrial abnormalities and low-grade inflammation can be seen and do not rule out the diagnosis of ALS. These findings could lend support to the notion that ALS is a complex and heterogeneous disorder.
Amyotrophic lateral Sclerosis; Mitochondria; Inflammation; Pathology and Muscle
Glioblastoma multiforme with an oligodendroglial component (GBMO) has been recognized in the World Health Organization classification—however, the diagnostic criteria, molecular biology, and clinical outcome of primary GBMO remain unclear. Our aim was to investigate whether primary GBMO is a distinct clinicopathological subgroup of GBM and to determine the relative frequency of prognostic markers such as loss of heterozygosity (LOH) on 1p and/or 19q, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and isocitrate dehydrogenase 1 (IDH1) mutation.
We examined 288 cases of primary GBM and assessed the molecular markers in 57 GBMO and 50 cases of other primary GBM, correlating the data with clinical parameters and outcome.
GBMO comprised 21.5% of our GBM specimens and showed significantly longer survival compared with our other GBM (12 mo vs 5.8 mo, P = .006); there was also a strong correlation with younger age at diagnosis (56.4 y vs 60.6 y, P = .005). Singular LOH of 19q (P = .04) conferred a 1.9-fold increased hazard of shorter survival. There was no difference in the frequencies of 1p or 19q deletion, MGMT promoter methylation, or IDH1 mutation (P = .8, P = 1.0, P = 1.0, respectively).
Primary GBMO is a subgroup of GBM associated with longer survival and a younger age group but shows no difference in the frequency of LOH of 1p/19q, MGMT, and IDH1 mutation compared with other primary GBM.
glioblastoma with an oligodendroglial component; histopathology; 1p/19q; IDH1; MGMT
Prosthetic hip-associated cobalt toxicity (PHACT) is gaining recognition due to the use of metal-on-metal total hip replacements. Identifying true toxicity from merely elevated cobalt levels can be extremely difficult due to the lack of available data. An extensive review of the medical literature was undertaken to characterize cobalt toxicity from prosthetic hips. As an objective approach to making the diagnosis of PHACT, we suggest the following criteria: (1) elevated serum or whole blood cobalt levels due to a prosthetic hip, (2) at least two test-confirmed findings consistent with cobalt toxicity, and (3) exclusion of other etiologies. Adhering to objective diagnostic data for PHACT is a realistic and prudent method by which to eliminate the subjectivity of vague or difficult to identify complaints. These diagnostic criteria are not meant to evaluate prosthetic hardware failure, but as a means to identify systemic cobalt toxicity. Finally, assessment of cobalt toxicity from prosthetic hips should be done in conjunction with a medical toxicologist.
Cobalt toxicity; Prosthetic hips; Metal-on-metal hip
Localizing a sound source involves the detection and integration of various spatial cues present in the sound waves at each ear. Previous studies indicate that the brain circuits underlying sound localization are calibrated by experience of the cues available to each individual. Plasticity in spatial hearing is most pronounced during development, but can also be demonstrated during adulthood under certain circumstances. Investigations into whether adult humans can adjust to reduced input in one ear and learn a new correspondence between interaural differences cues and directions in space have produced conflicting results. Here we show that humans of both sexes can relearn to localize broadband sounds with a “flat” spectrum in the horizontal plane after altering the spatial cues available by plugging one ear. In subjects who received daily training, localization accuracy progressively shifted back toward their pre-plug performance after one week of ear-plugging, whereas no improvement was seen if all trials were carried out on the same day. However, localization performance did not improve on a task that employed stimuli in which the source spectrum was randomized from trial to trial, indicating that monaural spectral cues are needed for plasticity. We also characterized the effects of the earplug on sensitivity to interaural time and level differences, and found no clear evidence for adaptation to these cues as the free-field localization performance improved. These findings suggest that the mature auditory system can accommodate abnormal inputs and maintain a stable spatial percept by reweighting different cues according to how informative they are.
Auditory; Binaural; Plasticity; Human; Spatial perception; Hearing; Training
Herding of sheep by dogs is a powerful example of one individual causing many unwilling individuals to move in the same direction. Similar phenomena are central to crowd control, cleaning the environment and other engineering problems. Despite single dogs solving this ‘shepherding problem’ every day, it remains unknown which algorithm they employ or whether a general algorithm exists for shepherding. Here, we demonstrate such an algorithm, based on adaptive switching between collecting the agents when they are too dispersed and driving them once they are aggregated. Our algorithm reproduces key features of empirical data collected from sheep–dog interactions and suggests new ways in which robots can be designed to influence movements of living and artificial agents.
collective motion; agent-based model; sheep; sheepdog
The koala, Phascolarctos cinereus, is a biologically unique and evolutionarily distinct Australian arboreal marsupial. The goal of this study was to sequence the transcriptome from several tissues of two geographically separate koalas, and to create the first comprehensive catalog of annotated transcripts for this species, enabling detailed analysis of the unique attributes of this threatened native marsupial, including infection by the koala retrovirus.
RNA-Seq data was generated from a range of tissues from one male and one female koala and assembled de novo into transcripts using Velvet-Oases. Transcript abundance in each tissue was estimated. Transcripts were searched for likely protein-coding regions and a non-redundant set of 117,563 putative protein sequences was produced. In similarity searches there were 84,907 (72%) sequences that aligned to at least one sequence in the NCBI nr protein database. The best alignments were to sequences from other marsupials. After applying a reciprocal best hit requirement of koala sequences to those from tammar wallaby, Tasmanian devil and the gray short-tailed opossum, we estimate that our transcriptome dataset represents approximately 15,000 koala genes. The marsupial alignment information was used to look for potential gene duplications and we report evidence for copy number expansion of the alpha amylase gene, and of an aldehyde reductase gene.
Koala retrovirus (KoRV) transcripts were detected in the transcriptomes. These were analysed in detail and the structure of the spliced envelope gene transcript was determined. There was appreciable sequence diversity within KoRV, with 233 sites in the KoRV genome showing small insertions/deletions or single nucleotide polymorphisms. Both koalas had sequences from the KoRV-A subtype, but the male koala transcriptome has, in addition, sequences more closely related to the KoRV-B subtype. This is the first report of a KoRV-B-like sequence in a wild population.
This transcriptomic dataset is a useful resource for molecular genetic studies of the koala, for evolutionary genetic studies of marsupials, for validation and annotation of the koala genome sequence, and for investigation of koala retrovirus. Annotated transcripts can be browsed and queried at http://koalagenome.org.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-786) contains supplementary material, which is available to authorized users.
Transcriptome; Koala; Phascolarctos cinereus; Koala retrovirus; Alpha amylase; Aldehyde reductase
Although many studies have examined the precedence effect (PE), few have tested whether it shows a buildup and breakdown in nonhuman animals comparable to that seen in humans. These processes are thought to reflect the ability of the auditory system to adjust to a listener’s acoustic environment, and their mechanisms are still poorly understood. In this study, ferrets were trained on a two-alternative forced-choice task to discriminate the azimuthal direction of brief sounds. In one experiment, pairs of noise bursts were presented from two loudspeakers at different interstimulus delays (ISDs). Results showed that localization performance changed as a function of ISD in a manner consistent with the PE being operative. A second experiment investigated buildup and breakdown of the PE by measuring the ability of ferrets to discriminate the direction of a click pair following presentation of a conditioning train. Human listeners were also tested using this paradigm. In both species, performance was better when the test clicks and conditioning train had the same ISD but deteriorated following a switch in the direction of the leading and lagging sounds between the conditioning train and test clicks. These results suggest that ferrets, like humans, experience a buildup and breakdown of the PE.
Our ability to document insect preference for semiochemicals is pivotal in pest control as these agents can improve monitoring and be deployed within integrated pest management programmes for more efficacious control of pest species. However, methods used to date have drawbacks that limit their utility. We present and test a new concept for determining insect motivation to move towards, or away from, semiochemicals by noting direction and speed of movement as animals work against a defined energy landscape (environmentally dependent variation in the cost of transport) requiring different powers to negotiate. We conducted trials with the pine weevils Hylobius abietis and peach-potato aphids Myzus persicae exposed to various attractants and repellents and placed so that they either moved up defined slopes against gravity or had to travel over variously rough surfaces.
Linear Mixed Models demonstrated clear reductions in travel speed by insects moving along increasingly energetically taxing energy landscapes but also that responses varied according to different semiochemicals, thus highlighting the value of energy landscapes as a new concept to help measure insect motivation to access or avoid different attractants or repellents across individuals.
New sensitive, detailed indicators of insect motivation derived from this approach should prove important in pest control across the world.
Cochlear implants (CIs) partially restore hearing to the deaf by directly stimulating the inner ear. In individuals fitted with CIs, lack of auditory experience due to loss of hearing before language acquisition can adversely impact outcomes. For example, adults with early-onset hearing loss generally do not integrate inputs from both ears effectively when fitted with bilateral CIs (BiCIs). Here, we used an animal model to investigate the effects of long-term deafness on auditory localization with BiCIs and approaches for promoting the use of binaural spatial cues. Ferrets were deafened either at the age of hearing onset or as adults. All animals were implanted in adulthood, either unilaterally or bilaterally, and were subsequently assessed for their ability to localize sound in the horizontal plane. The unilaterally implanted animals were unable to perform this task, regardless of the duration of deafness. Among animals with BiCIs, early-onset hearing loss was associated with poor auditory localization performance, compared with late-onset hearing loss. However, performance in the early-deafened group with BiCIs improved significantly after multisensory training with interleaved auditory and visual stimuli. We demonstrate a possible neural substrate for this by showing a training-induced improvement in the responsiveness of auditory cortical neurons and in their sensitivity to interaural level differences, the principal localization cue available to BiCI users. Importantly, our behavioral and physiological evidence demonstrates a facilitative role for vision in restoring auditory spatial processing following potential cross-modal reorganization. These findings support investigation of a similar training paradigm in human CI users.
auditory cortex; cochlear implant; cross-modal plasticity; hearing loss; multisensory; sound localization
Endovascular aneurysm repair (EVAR) is perhaps the most widely utilized surgical procedure for patients with large abdominal aortic aneurysms. This procedure is minimally invasive and reduces inpatient hospitalization requirements. The case involves a 72-year-old male who presented to the emergency department with right testicular ischemia two days following EVAR. Given the minimal inpatient hospitalization associated with this procedure, emergency physicians are likely to encounter associated complications. Ischemic and thromboembolic events following EVAR are extremely rare but require prompt vascular surgery intervention to minimize morbidity and mortality.
The sound-induced flash illusion (SIFI) is a multisensory perceptual phenomenon in which the number of brief visual stimuli perceived by an observer is influenced by the number of concurrently presented sounds. While the strength of this illusion has been shown to be modulated by the temporal congruence of the stimuli from each modality, there is conflicting evidence regarding its dependence upon their spatial congruence. We addressed this question by examining SIFIs under conditions in which the spatial reliability of the visual stimuli was degraded and different sound localization cues were presented using either free-field or closed-field stimulation. The likelihood of reporting a SIFI varied with the spatial cue composition of the auditory stimulus and was highest when binaural cues were presented over headphones. SIFIs were more common for small flashes than for large flashes, and for small flashes at peripheral locations, subjects experienced a greater number of illusory fusion events than fission events. However, the SIFI was not dependent on the spatial proximity of the audiovisual stimuli, but was instead determined primarily by differences in subjects' underlying sensitivity across the visual field to the number of flashes presented. Our findings indicate that the influence of auditory stimulation on visual numerosity judgments can occur independently of the spatial relationship between the stimuli.
auditory-visual interactions; sound-induced flash illusion; sound localization; visual sensitivity; signal detection theory
Verapamil; Cyclodextrin; N-acetylcysteine; Pediatric acute liver failure; Azithromycin; Sudden cardiac death; Dexmedetomidine; Withdrawal syndrome; Clonidine