The response to systemic stress is organized along the hypothalamic-pituitary-adrenal axis (HPA), whereas the response to a peripheral stress (solar radiation) is mediated by epidermal melanocytes (cells of neural crest origin) responsible for the pigmentary reaction. Melanocytes express proopiomelanocortin (POMC), corticotropin-releasing hormone (CRH), and CRH receptor-1 (CRH-R1) and can produce corticosterone. In the present study, incubation of normal epidermal melanocytes with CRH was found to trigger a functional cascade structured hierarchically and arranged along the same algorithm as in the HPA axis: CRH activation of CRH-R1 stimulated cAMP accumulation and increased POMC gene expression and production of ACTH. CRH and ACTH also enhanced production of cortisol and corticosterone, and cortisol production was also stimulated by progesterone. The chemical identity of the cortisol was confirmed by liquid chromatography-mass spectrometry (LC/MS2) with [corrected] mass spectrometry-mass spectrometry analyses. POMC gene silencing abolished the stimulatory effect of CRH on corticosteroid synthesis, indicating that this is indirect and mediated via production of ACTH. Thus the melanocyte response to CRH is highly organized along the same functional hierarchy as the HPA axis. This pattern demonstrates the fractal nature of the response to stress with similar activation sequence at the single-cell and whole body levels.

Persistent neural activity is a putative mechanism for the maintenance of working memories. Persistent activity relies on the activity of a distributed network of areas, but the differential contribution of each area remains unclear. We recorded single neurons in the human medial frontal cortex and the medial temporal lobe while subjects held up to three items in memory. We found persistently active neurons in both areas. Persistent activity of hippocampal and amygdala neurons was stimulus-specific, formed stable attractors, and was predictive of memory content. Medial frontal cortex persistent activity, on the other hand, was modulated by memory load and task set but was not stimulus-specific. Trial-by-trial variability in persistent activity in both areas was related to memory strength, because it predicted the speed and accuracy by which stimuli were remembered. This work reveals, in humans, direct evidence for a distributed network of persistently active neurons supporting working memory maintenance.

Distortion product otoacoustic emissions (DPOAE) were measured in normal-hearing and hearing-impaired human subjects. Analyses based on decision theory were used to evaluate DPOAE test performance. Specifically, relative operating characteristic (ROC) curves were constructed and the areas under these curves were used to estimate the extent to which normal and impaired ears could be correctly identified by these measures. DPOAE amplitude and DPOAE/noise measurements were able to distinguish between normal and impaired subjects at 4000, 8000, and, to a lesser extent, at 2000 Hz. The ability of these measures to distinguish between groups decreased, however, as frequency and audiometric criterion used to separate normal and hearing-impaired ears decreased. At 500 Hz, performance was no better than chance, regardless of the audiometric criterion for normal hearing. Cumulative distributions of misses (hearing-impaired ears incorrectly identified as normal hearing) and false alarms (normal-hearing ears identified as hearing impaired) were constructed and used to evaluate test performance for a range of hit rates (i.e., the percentage of correctly identified hearing-impaired ears). Depending on the desired hit rate, criterion values of -5 to -12 dB SPL for DPOAE amplitudes and 8 to 15 dB for DPOAE/noise accurately distinguished normal-hearing ears from those with thresholds greater than 20 dB HL for the two frequencies at which performance was best (4000 and 8000 Hz). It would appear that DPOAE measurements can be used to accurately identify the presence of high-frequency hearing loss, but are not accurate predictors of hearing status at lower frequencies, at least for the conditions of the present measurements.

The ability of transient-evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) to distinguish normal hearing from hearing impairment was evaluated in 180 subjects. TEOAEs were analyzed into octave or one-third octave bands for frequencies ranging from 500 to 4000 Hz. Decision theory was used to generate receiver operating characteristic (ROC) curves for each of three measurements (OAE amplitude, OAE/noise, reproducibility) for each OAE measure (octave TEOAEs, 1/3 octave TEOAEs, DPOAEs), for octave frequencies from 500 to 4000 Hz, and for seven audiometric criteria ranging from 10 to 40 dB HL. At 500 Hz, TEOAEs and DPOAEs were unable to separate normal from impaired ears. At 1000 Hz, both TEOAE measures were more accurate in identifying hearing status than DPOAEs. At 2000 Hz, all OAE measures performed equally well. At 4000 Hz, DPOAEs were better able to distinguish normal from impaired ears. Almost without exception, measurements of OAE/noise and reproducibility performed comparably and were superior to measurements of OAE amplitude, although the differences were small. TEOAEs analyzed into octave bands showed better performance than TEOAEs analyzed into 1/3 octaves. Under standard test conditions, OAE test performance appears to be limited by background noise, especially for the low frequencies.