Electromagnetic recordings reveal latency differences in speech and tone processing in humans.

Human auditory electromagnetic brain responses to sinusoidal (tone) and speech stimuli (Finnish vowel /a/ with two different glottal excitations) were studied with whole-head magnetoencephalogram (MEG) and electrodes placed on the subject's scalp. The frequency and intensity of the sinusoidal stimulus were optimally adjusted to match the spectra of the speech stimuli. Both tone and speech sounds elicited a prominent electric N1-P2 and magnetic N1m-P2m response complex. N1 and P2 amplitudes were larger to speech sounds than those to the tone. This amplitude enhancement was not as evident in the N1m and P2m obtained in MEG. Both the N1(m) and P2(m) latency always peaked earlier for the tone than for the vowels. The source origin of N1m for both the tone and speech stimuli was in the auditory cortex, there being no significant location differences as a function of stimulus type. N1m in the right hemisphere was anterior to that on the left, and P2m was anterior to N1m in both hemispheres. Varying the perceptual quality of the vowels by changing their glottal excitations (from "soft" /a/ to "pressed" /A/) had no effect on the response amplitudes or latencies. Thus, the present results show that only the latency behavior of N1(m) and P2(m) reliably dissociates speech and tone processing in humans. The findings are discussed in relation to previous observations on cortical processing of sinusoidal and vowel sounds and with regard to the glottal excitation in speech processing.

The periodic structure of vowel sounds is reflected in human electromagnetic brain responses.

Periodicity, which is caused by the vibration of the vocal folds, is an inherent feature of vowel sounds. Whether this periodic structure is reflected in cerebral processing of vowels was addressed via the use of non-invasive brain research methods combined with advanced stimulus production methodology. We removed the contribution of the source of the periodic structure, the glottal excitation produced by the vocal folds, from vowel stimuli and found that electromagnetic responses generated in the auditory cortex reflect this removal. The N1(m) amplitude decreased even though the rest of the acoustical features of the stimuli were identical. Thus, we conclude that speech production mechanisms have significant effects on human brain dynamics as reflected by magnetoencephalography and electroencephalograph.

Immunochemical and molecular biological studies on human placental cigarette smoke-inducible cytochrome P-450-dependent monooxygenase activities.

The induction of specific forms of cytochrome P-450 and P-450-associated xenobiotic-metabolizing monooxygenase activities by maternal cigarette smoking was characterized in human placenta employing polyclonal and monoclonal antibodies and recombinant DNA probes. The anti-BNF-B2 (prepared against rat liver P-450 induced by beta-naphthoflavone) inhibited about 60 per cent of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase activities (ERDE) in placental tissues from smoking mothers, whereas the anti-PB-B2 (to phenobarbital-induced rat liver P-450) was without significant inhibitory effect. Inhibition of 7-ethoxycoumarin O-deethylase (ECDE) by the anti-BNF-B2 was dependent on maternal smoking: the enzyme from non-smokers was not significantly inhibited, whereas the enzyme from smokers was variably inhibited by 15-60 per cent. The monoclonal antibodies towards the major 3-methylcholanthrene-inducible and phenobarbital-inducible rat liver P-450s (Mab 1-7-1 and 2-66-3, respectively) behaved similarly, except the inhibition was somewhat stronger if present. Antibody raised against rat liver NADPH-cytochrome P-450 oxido-reductase did not inhibit any activity studied. In immunoblotting experiments, the anti-reductase recognized the protein in human placental microsomes. However, neither anti-BNF-B2, anti-PB-B2 or Mab 1-7-1 or Mab 2-66-3 detected any proteins in human placental microsomes, regardless of smoking status. Northern blot hybridization analysis of placental RNA samples showed that only P-450IA1 mRNA existed in the placentas of smoking mothers with detectable ERDE activity. Despite the discrepancy between protein blotting and immunoinhibition data all other findings support the conclusion that maternal cigarette smoking induces the expression of the CYPIA1 gene (and not CYPIA2), resulting in an increased synthesis of P-450IA1 protein and increased AHH, ERDE and ECDE activities in human placenta.

Comparison of the formation of benzo[a]pyrene diolepoxide-DNA adducts in vitro by rat and human microsomes: evidence for the involvement of P-450IA1 and P-450IA2.

The involvement of cytochrome P-450 isozymes in the activation of benzo[a]pyrene (BP) by human placental and liver microsomes was studied in vitro using monoclonal antibodies (Mab) toward the major 3-methylcholanthrene (MC)-inducible and phenobarbital-inductible rat liver P-450 isozymes (Mab 1-7-1 and Mab 2-66-3, respectively). Microsomes from human placenta and liver and rat liver were incubated with BP and DNA, and BP-diolepoxide-DNA (BPDE-DNA) adducts were measured by synchronous fluorescence spectrophotometry (SFS). The only BP metabolite giving the same fluorescence peak as chemically modified BPDE-DNA was BP-7,8-dihydrodiol. Five (smokers) out of 29 human placentas (smokers and nonsmokers), and five out of nine human livers were able to metabolically activate BP to BPDE-DNA adducts in this system. The Mab 1-7-1 totally inhibited the formation of BPDE-DNA adducts in placental microsomal incubations. Inhibition using rat or human liver microsomes was 50-60% and about 90%, respectively. The Mab 2-66-3 had no effect in any of the microsome types. Adduct formation was inhibited more strongly and at lower concentrations of Mab 1-7-1 compared with the inhibition of AHH activity. This study is a clear indication of the major role of P-450IA1 (P-450c) in human placenta and probably P-450IA2 (P-450d) in human liver in BP activation, while other isozymes also take part in the activation in rat liver. Furthermore, this clearly indicates that AHH activity and BP activation are not necessarily associated.

Brain responses reveal the learning of foreign language phonemes.

Learning to speak a new language requires the formation of recognition patterns for the speech sounds specific to the newly acquired language. The present study demonstrates the dynamic nature of cortical memory representations for phonemes in adults by using the mismatch negativity (MMN) event-related potential. We studied Hungarian and Finnish subjects, dividing the Hungarians into a naive (no knowledge of Finnish) and a fluent (in Finnish) group. We found that the MMN for a contrast between two Finnish phonemes was elicited in the fluent Hungarians but not in the naive Hungarians. This result indicates that the fluent Hungarians developed cortical memory representations for the Finnish phoneme system that enabled them to preattentively categorize phonemes specific to this language.