Representation of Sound Objects within Early-Stage Auditory Areas: A Repetition Effect Study Using 7T fMRI.

Environmental sounds are highly complex stimuli whose recognition depends on the interaction of top-down and bottom-up processes in the brain. Their semantic representations were shown to yield repetition suppression effects, i. e. a decrease in activity during exposure to a sound that is perceived as belonging to the same source as a preceding sound. Making use of the high spatial resolution of 7T fMRI we have investigated the representations of sound objects within early-stage auditory areas on the supratemporal plane. The primary auditory cortex was identified by means of tonotopic mapping and the non-primary areas by comparison with previous histological studies. Repeated presentations of different exemplars of the same sound source, as compared to the presentation of different sound sources, yielded significant repetition suppression effects within a subset of early-stage areas. This effect was found within the right hemisphere in primary areas A1 and R as well as two non-primary areas on the antero-medial part of the planum temporale, and within the left hemisphere in A1 and a non-primary area on the medial part of Heschl's gyrus. Thus, several, but not all early-stage auditory areas encode the meaning of environmental sounds.

Neural detection of complex sound sequences in the absence of consciousness.

The neural response to a violation of sequences of identical sounds is a typical example of the brain's sensitivity to auditory regularities. Previous literature interprets this effect as a pre-attentive and unconscious processing of sensory stimuli. By contrast, a violation to auditory global regularities, i.e. based on repeating groups of sounds, is typically detectable when subjects can consciously perceive them. Here, we challenge the notion that global detection implies consciousness by testing the neural response to global violations in a group of 24 patients with post-anoxic coma (three females, age range 45-87 years), treated with mild therapeutic hypothermia and sedation. By applying a decoding analysis to electroencephalographic responses to standard versus deviant sound sequences, we found above-chance decoding performance in 10 of 24 patients (Wilcoxon signed-rank test, P < 0.001), despite five of them being mildly hypothermic, sedated and unarousable. Furthermore, consistently with previous findings based on the mismatch negativity the progression of this decoding performance was informative of patients' chances of awakening (78% predictive of awakening). Our results show for the first time that detection of global regularities at neural level exists despite a deeply unconscious state.

The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System.

In vitro differentiation of mesenchymal stromal cells (MSC) into osteocytes (human differentiated osteogenic cells, hDOC) before implantation has been proposed to optimize bone regeneration. However, a deep characterization of the immunological properties of DOC, including their effect on dendritic cell (DC) function, is not available. DOC can be used either as cellular suspension (detached, Det-DOC) or as adherent cells implanted on scaffolds (adherent, Adh-DOC). By mimicking in vitro these two different routes of administration, we show that both Det-DOC and Adh-DOC can modulate DC functions. Specifically, the weak downregulation of CD80 and CD86 caused by Det-DOC on DC surface results in a weak modulation of DC functions, which indeed retain a high capacity to induce T-cell proliferation and to generate CD4(+)CD25(+)Foxp3(+) T cells. Moreover, Det-DOC enhance the DC capacity to differentiate CD4(+)CD161(+)CD196(+) Th17-cells by upregulating IL-6 secretion. Conversely, Adh-DOC strongly suppress DC functions by a profound downregulation of CD80 and CD86 on DC as well as by the inhibition of TGF-β production. In conclusion, we demonstrate that different types of DOC cell preparation may have a different impact on the modulation of the host immune system. This finding may have relevant implications for the design of cell-based tissue-engineering strategies.

Roaring lions and chirruping lemurs: How the brain encodes sound objects in space.

The dual-stream model of auditory processing postulates separate processing streams for sound meaning and for sound location. The present review draws on evidence from human behavioral and activation studies as well as from lesion studies to argue for a position-linked representation of sound objects that is distinct both from the position-independent representation within the ventral/What stream and from the explicit sound localization processing within the dorsal/Where stream.

Electrostimulation mapping of comprehension of auditory and visual words.

In order to spare functional areas during the removal of brain tumours, electrical stimulation mapping was used in 90 patients (77 in the left hemisphere and 13 in the right; 2754 cortical sites tested). Language functions were studied with a special focus on comprehension of auditory and visual words and the semantic system. In addition to naming, patients were asked to perform pointing tasks from auditory and visual stimuli (using sets of 4 different images controlled for familiarity), and also auditory object (sound recognition) and Token test tasks. Ninety-two auditory comprehension interference sites were observed. We found that the process of auditory comprehension involved a few, fine-grained, sub-centimetre cortical territories. Early stages of speech comprehension seem to relate to two posterior regions in the left superior temporal gyrus. Downstream lexical-semantic speech processing and sound analysis involved 2 pathways, along the anterior part of the left superior temporal gyrus, and posteriorly around the supramarginal and middle temporal gyri. Electrostimulation experimentally dissociated perceptual consciousness attached to speech comprehension. The initial word discrimination process can be considered as an "automatic" stage, the attention feedback not being impaired by stimulation as would be the case at the lexical-semantic stage. Multimodal organization of the superior temporal gyrus was also detected since some neurones could be involved in comprehension of visual material and naming. These findings demonstrate a fine graded, sub-centimetre, cortical representation of speech comprehension processing mainly in the left superior temporal gyrus and are in line with those described in dual stream models of language comprehension processing.

Biological interpretation of genome-wide association studies using predicted gene functions.

The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes.

Investigating the functions of subregions within anterior hippocampus.

Previous functional MRI (fMRI) studies have associated anterior hippocampus with imagining and recalling scenes, imagining the future, recalling autobiographical memories and visual scene perception. We have observed that this typically involves the medial rather than the lateral portion of the anterior hippocampus. Here, we investigated which specific structures of the hippocampus underpin this observation. We had participants imagine novel scenes during fMRI scanning, as well as recall previously learned scenes from two different time periods (one week and 30 min prior to scanning), with analogous single object conditions as baselines. Using an extended segmentation protocol focussing on anterior hippocampus, we first investigated which substructures of the hippocampus respond to scenes, and found both imagination and recall of scenes to be associated with activity in presubiculum/parasubiculum, a region associated with spatial representation in rodents. Next, we compared imagining novel scenes to recall from one week or 30 min before scanning. We expected a strong response to imagining novel scenes and 1-week recall, as both involve constructing scene representations from elements stored across cortex. By contrast, we expected a weaker response to 30-min recall, as representations of these scenes had already been constructed but not yet consolidated. Both imagination and 1-week recall of scenes engaged anterior hippocampal structures (anterior subiculum and uncus respectively), indicating possible roles in scene construction. By contrast, 30-min recall of scenes elicited significantly less activation of anterior hippocampus but did engage posterior CA3. Together, these results elucidate the functions of different parts of the anterior hippocampus, a key brain area about which little is definitely known.