Sensorimotor learning in children and adults: Exposure to frequency-altered auditory feedback during speech production.

Auditory feedback plays an important role in the acquisition of fluent speech; however, this role may change once speech is acquired and individuals no longer experience persistent developmental changes to the brain and vocal tract. For this reason, we investigated whether the role of auditory feedback in sensorimotor learning differs across children and adult speakers. Participants produced vocalizations while they heard their vocal pitch predictably or unpredictably shifted downward one semitone. The participants' vocal pitches were measured at the beginning of each vocalization, before auditory feedback was available, to assess the extent to which the deviant auditory feedback modified subsequent speech motor commands. Sensorimotor learning was observed in both children and adults, with participants' initial vocal pitch increasing following trials where they were exposed to predictable, but not unpredictable, frequency-altered feedback. Participants' vocal pitch was also measured across each vocalization, to index the extent to which the deviant auditory feedback was used to modify ongoing vocalizations. While both children and adults were found to increase their vocal pitch following predictable and unpredictable changes to their auditory feedback, adults produced larger compensatory responses. The results of the current study demonstrate that both children and adults rapidly integrate information derived from their auditory feedback to modify subsequent speech motor commands. However, these results also demonstrate that children and adults differ in their ability to use auditory feedback to generate compensatory vocal responses during ongoing vocalization. Since vocal variability also differed across the children and adult groups, these results also suggest that compensatory vocal responses to frequency-altered feedback manipulations initiated at vocalization onset may be modulated by vocal variability.

ERP correlates of the magnitude of pitch errors detected in the human voice.

Auditory event-related potentials (ERP)s of the P1-N1-P2 complex are modulated when participants hear frequency-altered feedback (FAF) regarding their ongoing vocal productions. However, the relationship between feedback perturbation magnitudes and the resultant neural responses is at present unclear. In the present study, we exposed speakers to FAF of different magnitudes ranging from 0 to 400 cents. Vocal responses and P1-N1-P2-N2 ERPs were examined in an attempt to relate variation in the magnitude of the imposed feedback perturbation with variation in vocal and neural responses. Overall, vocal response magnitudes remained relatively consistent in response to smaller feedback perturbations (<250 cents), while larger feedback perturbations (>300 cents) resulted in decreased vocal response magnitudes. P1 amplitudes were found to increase in a non-specific manner in response to FAF. Conversely, N1 amplitudes displayed increased specificity: small feedback perturbations evoked one size of response, while larger feedback perturbations resulted in larger responses. The P2 component showed the most systematic amplitude modulation as feedback perturbation magnitude increased. A regression analysis highlighted the relationship between vocal response magnitude and P2 amplitude, with both vocal response magnitude and P2 amplitude increasing in response to perturbations between 50 and 250 cents, and then decreasing in response to larger perturbations. Although not generally observed in FAF studies, a robust N2 was also found; N2 amplitudes increased as stimulus magnitudes increased. The pattern of P1-N1-P2-N2 amplitude modulation in response to different magnitudes of FAF indicates that these components reflect processes involved in the detection and correction of unintended changes in auditory feedback during speech.

The anemia of the newborn induces erythropoietin expression in the developing mouse retina.

The hematopoietic hormone erythropoietin (Epo), regularly produced by the kidneys and the liver, is also expressed in neuronal tissue, where it has been found to mediate paracrine neuroprotective effects. In most studies exploring the rescue effects of Epo, apoptosis was exogenously induced by different cell death stimuli. Herein, we set out to study the expression and function of Epo in physiologically occurring apoptosis in a model of retinal development. We made use of an organotypic retinal wholemount culture system that resembles the physiological in vivo situation with cell connections still retained. Epo mRNA expression in the retina, liver, and kidney showed a significant increase during early development, coinciding with the anemia of the newborn. In the retina of Epo-green fluorescent protein transgenic mice, Epo-expressing cells were identified and found to be distributed in the retinal ganglion cell layer. Treatment of retinal wholemount cultures with recombinant Epo resulted in a significant decrease of apoptotic ganglion cells as well as photoreceptor cells throughout retinal development. Moreover, transforming growth factor-beta-induced apoptosis was completely antagonized by Epo when both factors were simultaneously applied. Investigations on the signaling pathway revealed a decrease in Bax mRNA levels in Epo-treated retinal cells. We conclude that Epo exerts wide and prolonged neuroprotective activity in physiologically occurring apoptosis and thus contributes to proper retinal development.

HPRT mutations in V79 Chinese hamster cells induced by accelerated Ni, Au and Pb ions.

Mutation induction by accelerated heavy ions to 6-TG resistance (HPRT system) in V79 Chinese hamster cells was investigated with Ni (6-630 Me V/u), Au (2.2, 8.7 Me V/u) and Pb ions (11.6-980 Me V/u) corresponding to a LET range between 180 and 12895 ke V/microns. Most experiments could only be performed once due to technical limitations using accelerator beam times. Survival curves were exponential, mutation induction curves linear with fluence. From their slopes inactivation- and mutation-induction cross-sections were derived. If they are plotted versus LET, single, ion-specific curves are obtained. It is shown that other parameters like ion energy and effective charge play an important role. In the case of Au and Pb ions the cross-sections follow a common line, since these ions have nearly the same atomic weight, so that they should have similar spatial ionization patterns in matter at the same energies. Calculated RBEs were higher for mutation induction than for killing for all LETs.