Mismatch response (MMR) in neonates: Beyond refractoriness.

In the adult auditory system, deviant detection and updating the representation of the environment is reflected by the event-related potential (ERP) component termed the mismatch negativity (MMN). MMN is elicited when a rare-pitch deviant stimulus is presented amongst frequent standard pitch stimuli. The same stimuli also elicit a similar discriminative ERP component in sleeping newborn infants (termed the mismatch response: MMR). Both the MMN and the MMR can be confounded by responses generated by differential refractoriness of frequency-selective neural populations. Employing a stimulus paradigm designed to minimize this confounding effect, newborns were presented with sequences of pure tones under two conditions: In the oddball block, rare deviant tones (500Hz; 10%) were delivered amongst frequent standards (700Hz; 90%). In the control block, a comparison tone (500Hz) was presented with the same probability as the deviant (10%) along with the four contextual tones (700Hz, 980Hz, 1372Hz, 1920.8Hz; 22.5% each). The significant difference found between the response elicited by the deviant and the comparison tone showed that the response elicited by the deviant in the oddball sequences cannot be fully explained by frequency-specific refractoriness of the neural generators. This shows that neonates process sounds in a context-dependent manner as well as strengthens the correspondence between the adult MMN and the infant MMR.

Predictive processing of pitch trends in newborn infants.

The notion of predictive sound processing suggests that the auditory system prepares for upcoming sounds once it has detected regular features within a sequence. Here we investigated whether predictive processes are operating at birth in the human auditory system. Event-related potentials (ERP) were recorded from healthy newborns to occasional ascending pitch steps occurring in the 2nd or the 5th position within trains of tones with otherwise monotonously descending pitch. If the trains were processed in a predictive manner only deviant pitch steps occurring in the later train position would elicit the discriminative mismatch response (MMR). Deviants delivered in the 5th but not in the 2nd position of the tone trains elicited a significant MMR response. These results suggest that newborns represent pitch trends within sound sequences and they process them in a predictive manner. This article is part of a Special Issue entitled SI: Prediction and Attention.

Detecting the temporal structure of sound sequences in newborn infants.

Most high-level auditory functions require one to detect the onset and offset of sound sequences as well as registering the rate at which sounds are presented within the sound trains. By recording event-related brain potentials to onsets and offsets of tone trains as well as to changes in the presentation rate, we tested whether these fundamental auditory capabilities are functional at birth. Each of these events elicited significant event-related potential components in sleeping healthy neonates. The data thus demonstrate that the newborn brain is sensitive to these acoustic features suggesting that infants are geared towards the temporal aspects of segregating sound sources, speech and music perception already at birth.

30 years' experience in the treatment of low-risk gestational trophoblastic neoplasia in Hungary.

OBJECTIVE: To review the clinical experience in the treatment of patients with low-risk gestational trophoblastic neoplasia (GTN) over the past 30 years in a national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2007, 302 patients with low-risk GTN were treated. The patients were directed to our institution from all parts of Hungary. The patients were 14 to 53 years of age with an average age of 28.3 years. Methotrexate (MTX)/folinic acid or actinomycin-D (Act-D) primary chemotherapy was selected based upon the patient's stage and prognostic score of GTN. RESULTS: Among 218 low-risk patients, 210 (96.3%) achieved remission as a result of MTX therapy. In 8 patients (3.7%), MTX-Act-D-cyclophosphamide (MAC) combination chemotherapy was needed to achieve complete remission, in some cases assisted by operation. Among 84 patients, 81 (96.4%) achieved remission as a result of Act-D therapy. In 3 cases (3.6%) complete remission was achieved by MAC combination chemotherapy. We detected metastases in 22.8% (69/302) of our low-risk patients. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% remission in cases of low-risk nonmetastatic and metastatic disease. CONCLUSION: Our data indicate that MTX/folinic acid or Act-D should be the primary treatment in patients with nonmetastatic or metastatic low-risk GTN. Importantly, patients with resistance to single-agent chemotherapy regularly achieve complete remission with MAC combination chemotherapy. Results show that patient care under the direction of experienced clinicians serves to optimize the opportunity for cure and minimize morbidity.