Adaptation In the Sensory Cortex Drives Bistable Switching During Auditory Stream Segregation

Current theories of perception emphasize the role of neural adaptation, inhibitory competition, and noise as key components that lead to switches in perception. Supporting evidence comes from neurophysiological findings of specific neural signatures in modality-specific and supramodal brain areas that appear to be critical to switches in perception. We used functional magnetic resonance imaging to study brain activity around the time of switches in perception while participants listened to a bistable auditory stream segregation stimulus, which can be heard as one integrated stream of tones or two segregated streams of tones. The auditory thalamus showed more activity around the time of a switch from segregated to integrated compared to time periods of stable perception of integrated; in contrast, the rostral anterior cingulate cortex and the inferior parietal lobule showed more activity around the time of a switch from integrated to segregated compared to time periods of stable perception of segregated streams, consistent with prior findings of asymmetries in brain activity depending on the switch direction. In sound-responsive areas in the auditory cortex, neural activity increased in strength preceding switches in perception and declined in strength over time following switches in perception. Such dynamics in the auditory cortex are consistent with the role of adaptation proposed by computational models of visual and auditory bistable switching, whereby the strength of neural activity decreases following a switch in perception, which eventually destabilizes the current percept enough to lead to a switch to an alternative percept

Age-Related Effects on Cross-Modal Duration Perception

Reliable duration perception of external events is necessary to coordinate perception with action, precisely discriminate speech, and for other daily functions. Visual duration perception can be heavily influenced by concurrent auditory signals; however, age-related effects on this process have received minimal attention. In the present study, we examined the effect of aging on duration perception by quantifying (1) duration discrimination thresholds, (2) auditory temporal dominance, and (3) visual duration expansion/compression percepts induced by an accompanying auditory stimulus of longer/shorter duration. Duration discrimination thresholds were significantly greater for visual than auditory tasks in both age groups, however there was no effect of age. While the auditory modality retained dominance in duration perception with age, older adults still performed worse than young adults when comparing durations of two target stimuli (e.g., visual) in the presence of distractors from the other modality (e.g., auditory). Finally, both age groups perceived similar visual duration compression, whereas older adults exhibited visual duration expansion over a wider range of auditory durations compared to their younger counterparts. Results are discussed in terms of multisensory integration and possible decision strategies that change with age

KSHV LANA upregulates the expression of epidermal growth factor like domain 7 to promote angiogenesis

Kaposi's sarcoma (KS) is a highly-vascularized tumor characterized by inflammation and extensive neo-angiogenesis. The KS tumor microenvironment is rich in inflammatory and pro-angiogenic cytokines. Here, we report that the expression of Epidermal growth factor-like domain 7 (EGFL7) is upregulated in Kaposi's sarcoma-associated herpes virus (KSHV) infected cells. EGFL7 is a secreted pro-angiogenic cytokine that has been implicated in angiogenesis and the proliferation of endothelial cells during many pathological conditions. Our data show that KS tumors as well as primary effusion lymphoma cells have increased levels of EGFL7 compared to the uninfected cells. We determined that the expression of a KSHV latent protein, LANA (latency-associated nuclear antigen), is the main viral factor responsible for this upregulation. The modulation of EGFL7 expression by LANA involves sequestration of death domain-associated protein 6 (Daxx) from the EGFL7 promoter. Daxx acts as a suppressor of promoter activity by binding to the avian erythroblastosis virus E26 oncogene homolog 1 (Ets-1), which is the core transcription factor required for the expression of EGFL7. We additionally show that the upregulation of EGFL7 by LANA contributes to the promotion of angiogenesis since siRNA-mediated knockdown of EGFL7 reduced in vitro tubulogenesis in LANA-expressing HUVEC cells. EGFL7 promotes angiogenesis through autocrine as well as paracrine mechanisms as the supernatant from LANA expressing cells depleted of EGFL7 showed reduced tubulogenesis. This study for the first time demonstrates EGFL7 to be an important angiogenic molecule secreted during KSHV infection that could be exploited for blocking KSHV associated malignancies in conjugation with other anti-angiogenic therapies