Deafness induces complete crossmodal plasticity in a belt region of dorsal auditory cortex.

Many neural areas, where patterned activity is lost following deafness, have the capacity to become activated by the remaining sensory systems. This crossmodal plasticity can be measured at perceptual/behavioural as well as physiological levels. The dorsal zone (DZ) of auditory cortex of deaf cats is involved in supranormal visual motion detection, but its physiological level of crossmodal reorganisation is not well understood. The present study of early-deaf DZ (and hearing controls) used multiple single-channel recording methods to examine neuronal responses to visual, auditory, somatosensory and combined stimulation. In early-deaf DZ, no auditory activation was observed, but 100% of the neurons were responsive to visual cues of which 21% were also influenced by somatosensory stimulation. Visual and somatosensory responses were not anatomically organised as they are in hearing cats, and fewer multisensory neurons were present in the deaf condition. These crossmodal physiological results closely correspond with and support the perceptual/behavioural enhancements that occur following hearing loss.

Patient Eligibility for Established and Novel Guideline-Directed Medical Therapies After Acute Heart Failure Hospitalization.

BACKGROUND: Acute heart failure (AHF) hospitalization presents an opportunity to optimize pharmacotherapy to improve outcomes. OBJECTIVES: This study's aim was to define eligibility for initiation of guideline-directed medical therapy and newer heart failure (HF) agents from recent clinical trials in the AHF population. METHODS: The authors analyzed patients with an AHF admission within the CAN-HF (Canadian Heart Failure) registry between January 2017 and April 2020. Heart failure with reduced ejection fraction (HFrEF) was defined as left ventricular ejection fraction (LVEF) ≤40% and heart failure with preserved ejection fraction (HFpEF) as LVEF >40%. Eligibility was assessed according to the major society guidelines or enrollment criteria from recent landmark clinical trials. RESULTS: A total of 809 patients with documented LVEF were discharged alive from hospital: 455 with HFrEF and 354 with HFpEF; of these patients, 284 had a de novo presentation and 525 had chronic HF. In HFrEF patients, eligibility for therapies was 73.6% for angiotensin receptor-neprilysin inhibitors (ARNIs), 94.9% for beta-blockers, 84.4% for mineralocorticoid receptor antagonists (MRAs), 81.1% for sodium-glucose cotransporter-2 (SGLT2) inhibitors, and 15.6% for ivabradine. Additionally, 25.9% and 30.1% met trial criteria for vericiguat and omecamtiv mecarbil, respectively. Overall, 71.6% of patients with HFrEF (75.5% de novo, 69.5% chronic HF) were eligible for foundational quadruple therapy. In the HFpEF population, 37.6% and 59.9% were eligible for ARNIs and SGLT2 inhibitors based on recent trial criteria, respectively. CONCLUSIONS: The majority of patients admitted with AHF are eligible for foundational quadruple therapy and additional novel medications across a spectrum of HF phenotypes.

A comparison of multisensory features of two auditory cortical areas: primary (A1) and higher-order dorsal zone (DZ).

From myriads of ongoing stimuli, the brain creates a fused percept of the environment. This process, which culminates in perceptual binding, is presumed to occur through the operations of multisensory neurons that occur throughout the brain. However, because different brain areas receive different inputs and have different cytoarchitechtonics, it would be expected that local multisensory features would also vary across regions. The present study investigated that hypothesis using multiple single-unit recordings from anesthetized cats in response to controlled, electronically-generated separate and combined auditory, visual, and somatosensory stimulation. These results were used to compare the multisensory features of neurons in cat primary auditory cortex (A1) with those identified in the nearby higher-order auditory region, the Dorsal Zone (DZ). Both regions exhibited the same forms of multisensory neurons, albeit in different proportions. Multisensory neurons exhibiting excitatory or inhibitory properties occurred in similar proportions in both areas. Also, multisensory neurons in both areas expressed similar levels of multisensory integration. Because responses to auditory cues alone were so similar to those that included non-auditory stimuli, it is proposed that this effect represents a mechanism by which multisensory neurons subserve the process of perceptual binding.

Multisensory responses in a belt region of the dorsal auditory cortical pathway.

A basic function of the cerebral cortex is to receive and integrate information from different sensory modalities into a comprehensive percept of the environment. Neurons that demonstrate multisensory convergence occur across the necortex but are especially prevalent in higher order association areas. However, a recent study of a cat higher order auditory area, the dorsal zone (DZ) of auditory cortex, did not observe any multisensory features. Therefore, the goal of the present investigation was to address this conflict using recording and testing methodologies that are established for exposing and studying multisensory neuronal processing. Among the 482 neurons studied, we found that 76.6% were influenced by non-auditory stimuli. Of these neurons, 99% were affected by visual stimulation, but only 11% by somatosensory. Furthermore, a large proportion of the multisensory neurons showed integrated responses to multisensory stimulation, constituted a majority of the excitatory and inhibitory neurons encountered (as identified by the duration of their waveshape) and exhibited a distinct spatial distribution within DZ. These findings demonstrate that the DZ of auditory cortex robustly exhibits multisensory properties and that the proportions of multisensory neurons encountered are consistent with those identified in other higher order cortices.

A Food, a Bite, a Sip: How Much Allergen Is in That?

Detailed information about the amount of allergenic protein ingested by the patient prior to an allergic reaction yields valuable information for the diagnosis, guidance and management of food allergy. However, the exact amount of ingredients is often not declared on the label. In this study the feasibility was studied for estimating the amount of allergenic protein from milk, eggs, peanuts and hazelnuts in frequently consumed composite and non-composite foods and per bite or sip size in different age groups in the Netherlands. Foods containing milk, egg, peanut or hazelnut most frequently consumed were selected for the age groups 2-3, 4-6 and 19-30 years. If the label did not yield clear information, the amount of allergenic protein was estimated based on food labels. Bite or sip sizes were determined in these age groups in 30 different foods. The amount of allergenic protein could be estimated in 47/70 (67%) of composite foods, which was complex. Estimated protein content of milk, egg, peanut and hazelnut was 2-3 g for most foods but varied greatly from 3 to 8610 mg and may be below threshold levels of the patient. In contrast, a single bite or sip can contain a sufficient amount of allergenic protein to elicit an allergic reaction. Bite and sip sizes increased with age. In every day practice it is hard to obtain detailed and reliable information about the amount of allergenic protein incorporated in composite foods. We encourage companies to disclose the amount of common allergenic foods on their labels.

Origin of the thalamic projection to dorsal auditory cortex in hearing and deafness.

While it is now well accepted that the brain reorganizes following sensory loss, the neural mechanisms that give rise to this plasticity are not well understood. Anatomical tract tracing studies have begun to shed light on the structural underpinnings of cross-modal reorganization by comparing cerebral connectivity in sensory-deprived animals to that of their non-deprived counterparts. However, so far, full documentation of connectional patterns within hearing, congenitally deaf, as well as animals deafened early versus later in life exist only for primary auditory cortex, a region not known to undergo cross-modal reorganization in the deaf. The purpose of the present investigation was to examine thalamo-cortical patterns of connectivity in hearing, late- and early-deafened cats to the dorsal zone (DZ), a region of auditory cortex that cross-modally reorganizes to mediate enhanced visual motion perception following deafness. In hearing cats, the largest projections to DZ arose from the dorsal division of the medial geniculate body (MGB) with lesser projections originating in the medial and ventral MGB and from the suprageniculate and the lateral posterior nuclei. In general, while some variations in the strength of specific thalamic projections were noted, the pattern of projections arising from the thalamus in early- and late-deafened animals remained consistent with that of hearing subjects. These results complement the existing thalamic connectivity data described for congenitally deaf animals, which together demonstrate that thalamo-cortical connectivity patterns to DZ are conserved following deafness, irrespective of the time of onset and etiology of deafness.

Amplified somatosensory and visual cortical projections to a core auditory area, the anterior auditory field, following early- and late-onset deafness.

Cross-modal reorganization following the loss of input from a sensory modality can recruit sensory-deprived cortical areas to process information from the remaining senses. Specifically, in early-deaf cats, the anterior auditory field (AAF) is unresponsive to auditory stimuli but can be activated by somatosensory and visual stimuli. Similarly, AAF neurons respond to tactile input in adult-deafened animals. To examine anatomical changes that may underlie this functional adaptation following early or late deafness, afferent projections to AAF were examined in hearing cats, and cats with early- or adult-onset deafness. Unilateral deposits of biotinylated dextran amine were made in AAF to retrogradely label cortical and thalamic afferents to AAF. In early-deaf cats, ipsilateral neuronal labeling in visual and somatosensory cortices increased by 329% and 101%, respectively. The largest increases arose from the anterior ectosylvian visual area and the anterolateral lateral suprasylvian visual area, as well as somatosensory areas S2 and S4. Consequently, labeling in auditory areas was reduced by 36%. The age of deafness onset appeared to influence afferent connectivity, with less marked differences observed in late-deaf cats. Profound changes to visual and somatosensory afferent connectivity following deafness may reflect corticocortical rewiring affording acoustically deprived AAF with cross-modal functionality.

Effects of core auditory cortex deactivation on neuronal response to simple and complex acoustic signals in the contralateral anterior auditory field.

Interhemispheric communication has been implicated in various functions of sensory signal processing and perception. Despite ample evidence demonstrating this phenomenon in the visual and somatosensory systems, to date, limited functional assessment of transcallosal transmission during periods of acoustic signal exposure has hindered our understanding of the role of interhemispheric connections between auditory cortical fields. Consequently, the present investigation examines the impact of core auditory cortical field deactivation on response properties of contralateral anterior auditory field (AAF) neurons in the felis catus. Single-unit responses to simple and complex acoustic signals were measured across AAF before, during, and after individual and combined cooling deactivation of contralateral primary auditory cortex (A1) and AAF neurons. Data analyses revealed that on average: 1) interhemispheric projections from core auditory areas to contralateral AAF neurons are predominantly excitatory, 2) changes in response strength vary based on acoustic features, 3) A1 and AAF projections can modulate AAF activity differently, 4) decreases in response strength are not specific to particular cortical laminae, and 5) contralateral inputs modulate AAF neuronal response thresholds. Collectively, these observations demonstrate that A1 and AAF neurons predominantly modulate AAF response properties via excitatory projections.

Dissociable influences of primary auditory cortex and the posterior auditory field on neuronal responses in the dorsal zone of auditory cortex.

Current models of hierarchical processing in auditory cortex have been based principally on anatomical connectivity while functional interactions between individual regions have remained largely unexplored. Previous cortical deactivation studies in the cat have addressed functional reciprocal connectivity between primary auditory cortex (A1) and other hierarchically lower level fields. The present study sought to assess the functional contribution of inputs along multiple stages of the current hierarchical model to a higher order area, the dorsal zone (DZ) of auditory cortex, in the anaesthetized cat. Cryoloops were placed over A1 and posterior auditory field (PAF). Multiunit neuronal responses to noise burst and tonal stimuli were recorded in DZ during cortical deactivation of each field individually and in concert. Deactivation of A1 suppressed peak neuronal responses in DZ regardless of stimulus and resulted in increased minimum thresholds and reduced absolute bandwidths for tone frequency receptive fields in DZ. PAF deactivation had less robust effects on DZ firing rates and receptive fields compared with A1 deactivation, and combined A1/PAF cooling was largely driven by the effects of A1 deactivation at the population level. These results provide physiological support for the current anatomically based model of both serial and parallel processing schemes in auditory cortical hierarchical organization.

Modified areal cartography in auditory cortex following early- and late-onset deafness.

Cross-modal plasticity following peripheral sensory loss enables deprived cortex to provide enhanced abilities in remaining sensory systems. These functional adaptations have been demonstrated in cat auditory cortex following early-onset deafness in electrophysiological and psychophysical studies. However, little information is available concerning any accompanying structural compensations. To examine the influence of sound experience on areal cartography, auditory cytoarchitecture was examined in hearing cats, early-deaf cats, and cats with late-onset deafness. Cats were deafened shortly after hearing onset or in adulthood. Cerebral cytoarchitecture was revealed immunohistochemically using SMI-32, a monoclonal antibody used to distinguish auditory areas in many species. Auditory areas were delineated in coronal sections and their volumes measured. Staining profiles observed in hearing cats were conserved in early- and late-deaf cats. In all deaf cats, dorsal auditory areas were the most mutable. Early-deaf cats showed further modifications, with significant expansions in second auditory cortex and ventral auditory field. Borders between dorsal auditory areas and adjacent visual and somatosensory areas were shifted ventrally, suggesting expanded visual and somatosensory cortical representation. Overall, this study shows the influence of acoustic experience in cortical development, and suggests that the age of auditory deprivation may significantly affect auditory areal cartography.

Cross-modal reorganization of cortical afferents to dorsal auditory cortex following early- and late-onset deafness.

Cat auditory cortex is known to undergo cross-modal reorganization following deafness, such that behavioral advantages in visual motion detection are abolished when a specific region of deaf auditory cortex, the dorsal zone (DZ), is deactivated. The purpose of the present investigation was to examine the connectional adaptations that might subserve this plasticity. We deposited biotinylated dextran amine (BDA; 3,000 MW), a retrograde tracer, unilaterally into the posterior portion of the suprasylvian fringe, corresponding to area DZ of hearing, early-deafened (onset <1 month), and late-deafened (onset >3 months) cats to reveal cortical afferent projections. Overall, the pattern of cortical projections to DZ was similar in both hearing and deafened animals. However, there was a progressive increase in projection strength among hearing and late- and early-deafened cats from an extrastriate visual cortical region known to be involved in the processing of visual motion, the posterolateral lateral suprasylvian area (PLLS). Additionally, although no such change was documented for the posteromedial lateral suprasylvian area (PMLS), labeled neurons were present within a subregion of PMLS devoted to foveal vision in both late- and early-deafened animals but not in hearing controls. PMLS is also an extrastriate visual motion processing area and is widely considered to be the homolog of primate middle temporal area. No changes in auditory cortical connectivity were observed among groups. These observations suggest that amplified cortical projections from extrastriate visual areas involved in visual motion processing to DZ may contribute to the cross-modal reorganization that functionally manifests as superior visual motion detection ability in the deaf animal.

Influence of core auditory cortical areas on acoustically evoked activity in contralateral primary auditory cortex.

In contrast to numerous studies of transcallosal communication in visual and somatosensory cortices, the functional properties of interhemispheric connections between auditory cortical fields have not been widely scrutinized. Therefore, the purpose of the present investigation was to measure the magnitude and type (inhibitory/excitatory) of modulatory properties of core auditory fields on contralateral primary auditory cortex (A1) activity. We combined single-unit neuronal recordings with reversible cooling deactivation techniques to measure variations in contralateral A1 response levels during A1, anterior auditory field (AAF), or simultaneous A1 and AAF neuronal discharge suppression epochs in cat auditory cortex. Cortical activity was evoked by presentation of pure tones, noise bursts, and frequency-modulated (FM) sweeps before, during, and after cortical deactivation periods. Comparisons of neuronal response changes before and during neuronal silencing revealed three major findings. First, deactivation of A1 and AAF-induced significant peak response reductions in contralateral A1 activity during simple (tonal) and complex (noise bursts and FM sweeps) acoustic exposure. Second, decreases in A1 neuronal activity appear to be in agreement with anatomical laminar termination patterns emanating from contralateral auditory cortex fields. Third, modulatory properties of core auditory areas lack hemispheric lateralization. These findings demonstrate that during periods of acoustic exposure, callosal projections emanating from core auditory areas modulate A1 neuronal activity via excitatory inputs.