Integration of Visual Information in Auditory Cortex Promotes Auditory Scene Analysis through Multisensory Binding.

How and where in the brain audio-visual signals are bound to create multimodal objects remains unknown. One hypothesis is that temporal coherence between dynamic multisensory signals provides a mechanism for binding stimulus features across sensory modalities. Here, we report that when the luminance of a visual stimulus is temporally coherent with the amplitude fluctuations of one sound in a mixture, the representation of that sound is enhanced in auditory cortex. Critically, this enhancement extends to include both binding and non-binding features of the sound. We demonstrate that visual information conveyed from visual cortex via the phase of the local field potential is combined with auditory information within auditory cortex. These data provide evidence that early cross-sensory binding provides a bottom-up mechanism for the formation of cross-sensory objects and that one role for multisensory binding in auditory cortex is to support auditory scene analysis.

Acute Inactivation of Primary Auditory Cortex Causes a Sound Localisation Deficit in Ferrets.

The objective of this study was to demonstrate the efficacy of acute inactivation of brain areas by cooling in the behaving ferret and to demonstrate that cooling auditory cortex produced a localisation deficit that was specific to auditory stimuli. The effect of cooling on neural activity was measured in anesthetized ferret cortex. The behavioural effect of cooling was determined in a benchmark sound localisation task in which inactivation of primary auditory cortex (A1) is known to impair performance. Cooling strongly suppressed the spontaneous and stimulus-evoked firing rates of cortical neurons when the cooling loop was held at temperatures below 10°C, and this suppression was reversed when the cortical temperature recovered. Cooling of ferret auditory cortex during behavioural testing impaired sound localisation performance, with unilateral cooling producing selective deficits in the hemifield contralateral to cooling, and bilateral cooling producing deficits on both sides of space. The deficit in sound localisation induced by inactivation of A1 was not caused by motivational or locomotor changes since inactivation of A1 did not affect localisation of visual stimuli in the same context.

Where are multisensory signals combined for perceptual decision-making?

Multisensory integration is observed in many subcortical and cortical locations including primary and non-primary sensory cortex, and higher cortical areas including frontal and parietal cortex. During unisensory perceptual tasks many of these same brain areas show neural signatures associated with decision-making. It is unclear whether multisensory representations in sensory cortex directly inform decision-making in a multisensory task, or if cross-modal signals are only combined after the accumulation of unisensory evidence at a final decision-making stage in higher cortical areas. Manipulations of neuronal activity are required to establish causal roles for given brain regions in multisensory perceptual decision-making, and so far indicate that distributed networks underlie multisensory decision-making. Understanding multisensory integration requires synthesis of small-scale pathway specific and large-scale network level manipulations.

Oxycodone and Naloxone Combination: A 12-Week Follow-up in 20 Patients Shows Effective Analgesia Without Opioid-Induced Bowel Dysfunction.

INTRODUCTION: Opioid analgesics are widely regarded to be highly effective but are equally known for their side effects on the bowel. A new combination of the opioid analgesic oxycodone and naloxone has been developed to combat opioid-induced bowel dysfunction (OIBD) whilst still being effective as an analgesic. The aim of this observational study was to assess the analgesic efficacy of this new combination and to analyze its effect on bowel function. METHODS: Twenty-six patients underwent a trial of this new combination, with 21 patients reaching week 8 and 18 reaching week 12. RESULTS: A significant reduction was seen in the pain severity score at weeks 4, 8, and 12 (P < 0.05), and a significant improvement in the bowel function index was again seen at these points (P < 0.001 at week 4 and 12, P < 0.05 at week 8). In the patients' global impression of change, 83.3% of patients rated the new medication as an improvement compared to their previous regimen, and 87.5% rated it overall as "good" or "very good." CONCLUSION: This small single-center study suggests that the use of ONC in selected patients could lead to an improvement in pain severity and pain interference with a significant improvement in OIBD. Compliance with the combination is good, and it is generally well tolerated.

Modified protein expression in the tectorial membrane of the cochlea reveals roles for the striated sheet matrix.

The tectorial membrane (TM) of the mammalian cochlea is a complex extracellular matrix which, in response to acoustic stimulation, displaces the hair bundles of outer hair cells (OHCs), thereby initiating sensory transduction and amplification. Here, using TM segments from the basal, high-frequency region of the cochleae of genetically modified mice (including models of human hereditary deafness) with missing or modified TM proteins, we demonstrate that frequency-dependent stiffening is associated with the striated sheet matrix (SSM). Frequency-dependent stiffening largely disappeared in all three TM mutations studied where the SSM was absent either entirely or at least from the stiffest part of the TM overlying the OHCs. In all three TM mutations, dissipation of energy is decreased at low (<8 kHz) and increased at high (>8 kHz) stimulus frequencies. The SSM is composed of polypeptides carrying fixed charges, and electrostatic interaction between them may account for frequency-dependent stiffness changes in the material properties of the TM. Through comparison with previous in vivo measurements, it is proposed that implementation of frequency-dependent stiffening of the TM in the OHC attachment region facilitates interaction among tones, backward transmission of energy, and amplification in the cochlea.

The vestibular system mediates sensation of low-frequency sounds in mice.

The mammalian inner ear contains sense organs responsible for detecting sound, gravity and linear acceleration, and angular acceleration. Of these organs, the cochlea is involved in hearing, while the sacculus and utriculus serve to detect linear acceleration. Recent evidence from birds and mammals, including humans, has shown that the sacculus, a hearing organ in many lower vertebrates, has retained some of its ancestral acoustic sensitivity. Here we provide not only more evidence for the retained acoustic sensitivity of the sacculus, but we also found that acoustic stimulation of the sacculus has behavioral significance in mammals. We show that the amplitude of an elicited auditory startle response is greater when the startle stimuli are presented simultaneously with a low-frequency masker, including masker tones that are outside the sensitivity range of the cochlea. Masker-enhanced auditory startle responses were also observed in otoconia-absent Nox3 mice, which lack otoconia but have no obvious cochlea pathology. However, masker enhancement was not observed in otoconia-absent Nox3 mice if the low-frequency masker tones were outside the sensitivity range of the cochlea. This last observation confirms that otoconial organs, most likely the sacculus, contribute to behavioral responses to low-frequency sounds in mice.