Changes in auditory cortex and the development of mismatch negativity between 2 and 6 months of age.

Evoked responses to stimulus deviance were compared in infants between 2 and 6 months of age. A deviant stimulus containing a short silent gap occasionally replaced a repeating standard stimulus matched in duration, intensity and approximate spectral content. At two months, the standard stimuli evoked only a positive slow wave, and its amplitude was increased in response to the deviant stimuli. By 6 months, the deviant stimuli evoked an increased negativity at approximately 200 ms, similar to the mismatch negativity (MMN) response in adults. The results are considered with respect to layer-specific cortical maturation during this period.     

Short-Term Habituation and Dishabituation of the Mismatch Negativity of the ERP

Standard tones of 1000 Hz and deviant tones of 1250 Hz were presented in random order, 1 stimulus/second. The probabilities of the standards and deviants were 90% and 10%, respectively. In one condition the subject counted the deviant stimuli and in the other condition he/she read a comic book. ERPs were separately averaged to 1) the standard preceding the deviant, 2) the “first deviant” preceded by at least 4 standards, 3) the “second deviant” (an occasional deviant immediately following the “first deviant”), 4) the first and 5) the second standard following the “first deviant,” 6) the first and 7) the second standard following the “second deviant.” It was found that the mismatch negativity evoked in both conditions by the first deviant was considerably larger than to the second deviant. Also the first standard following the first deviant evoked the mismatch negativity. The results are discussed in terms of parallel neuronal models of the stimuli as reflected by the mismatch negativity.     

Association of attention deficit hyperactivity disorder-related psychopathology and personality traits with the serotonin transporter promoter region polymorphism

A two-tone oddball procedure was employed to examine the effect of a phonemic category on the mismatch negativity (MMN). One of the stimuli was a phoneme prototype of Japanese /e/, and the other, [e/?], which was perceived by Japanese participants as showing deviance from typicality but is nonetheless included in the category /e/. As control stimuli, a pair of pure tones (1940 and 1794 Hz), corresponding to the F2 frequencies of /e/ and [e/?], respectively, was presented within the same oddball procedure. The MMN for deviant [e/?] revealed greater amplitude than that of deviant /e/, although there was no significant difference in amplitude between the pure tones. The results suggest that a phonemic category determines the auditory sensory memory.     

The Effects of Channel-Selective Attention on the Mismatch Negativity Wave Elicited by Deviant Tones

The mismatch negativity (MMN) is an event-related brain potential elicited by infrequent, physically deviant sounds in a sequence of repetitive auditory stimuli. Two dichotic listening experiments that were designed to optimize the selective focusing of attention provided a strong test of Näätänen's proposal that the MMN is unaffected by attention and reflects the operation of a strongly automatic mismatch detection system. In Experiment 1, tones were presented at intervals of 120-320 ms, and the deviant tones (intensity decrements) in both the attended and unattended ears elicited negative waves consistent in waveshape, latency, and distribution with previously described MMNs. In contrast to previous reports, however, the MMN elicited by the unattended-channel deviant was markedly reduced (peak amplitude of less than 1 μV) relative to the corresponding negative wave elicited by the attended-channel deviants (3–4 μV), as well as relative to previously reported MMNs (3–6 μV) elicited by comparable deviations in stimulus intensity. In Experiment 2, which employed interstimulus intervals of 65–205 ms, the unattended-channel MMN elicited by the deviant fainter tones was barely discernible, whereas the corresponding attended-channel negativity was again about 3-4 μV.
These findings call into question the assertion that the auditory mismatch detection process and the associated MMN wave are wholly independent of attentional influence. Rather, these data provide evidence that the processing of stimuli in unattended channels can be attenuated or gated at an early sensory level under conditions of highly focused auditory selective attention.     

Transient Transmission of Hepatitis C Virus from Mothers to Newborns

 A study was performed in Israel to determine the rate of mother-to-infant HCV transmission in newborns at risk. A group of 22 HCV-infected mothers and their 23 newborns were followed up from early after birth by testing their serum for the presence of HCV antibodies and HCV-RNA. Antibody against HCV was detected in the blood of all newborns immediately after birth, but dropped to low or undetectable levels by 7 months of age. HCV-RNA was detected 2 days after birth in the blood of five infants (22%) but fell to undetectable levels by 6 months. HCV-HVR1 sequence analysis performed in one mother-infant pair on the second day after birth revealed two nucleotide changes. Two months later the same sequence was detected again in the HVR1, suggesting a very low replication rate. Thus, the study showed that vertically transmitted HCV was eliminated in all newborn infants by 6 months after delivery, with concomitant disappearance of HCV antibodies. The mechanism of HCV elimination in newborns at risk remains to be elucidated.     

Healthy Preterm Newborns Show an Increased Frequency of CD4+CD25highCD127lowFOXP3+ Regulatory T Cells with a Naive Phenotype and High Expression of Gut‐Homing Receptors

Treg cells are crucial to prevent immune dysregulation, but little is known about the frequency of these cells in neonates, particularly in very/moderate and late preterm newborns studied as separate groups. The CD4⁺CD25^hiCD127^loFOXP3⁺Treg population was phenotypically characterized to assess maturation markers and gut‐homing integrins by flow cytometry in the cord blood of healthy preterm newborns born at 30–33^6/7 gestation weeks (Group 1), at 34–36^6/7 gestation weeks (Group 2) and term newborns born at 37–41 gestation weeks (Group 3), compared to healthy adults. An inverse correlation of the Treg percentage and gestational age was found, with significantly higher frequencies in Group 1 compared to Groups 2 and 3 and in Group 2 compared to Group 3, and significantly higher Treg frequencies and numbers in the neonates compared to the adults. All of the newborns exhibited increased Treg frequencies with a naive phenotype compared to adults. Cytotoxic T‐lymphocyte‐associated protein 4 CTLA‐4 expression in the naive Treg was decreased in both preterm groups compared with those from term newborns and adults, and in the memory Treg from Group 1 compared with the other groups. The frequencies of Treg expressing α4β7 and α4β1 integrins were higher in both preterm groups, but significantly different only in Group 1, when compared with those from the term newborns and the adults. In conclusion, although a high frequency of Treg is present in newborns, an immature phenotype with a higher expression of CD45RA and α4β7/α4β1 and a lower expression of CTLA‐4 is found, particularly in the very preterm group.     

Temporal grouping affects the automatic processing of deviant sounds

The present study investigates the influence of auditory temporal grouping on automatic sound processing. We compared the mismatch negativity (MMN) event-related potential elicited by successive deviant tones in a condition in which sounds were organized in tone pairs with respective MMN obtained in a non-paired sequence. When successive deviants belonged to different tone pairs the second deviant elicited a higher MMN amplitude than the corresponding deviant in the non-paired condition. Moreover, this temporal grouping had immediate effects on the extraction of rules as revealed by the finding that first and single deviants at the second position of a tone pair elicited larger MMNs than corresponding deviants in the non-paired condition or first and single deviants at the first position of a tone pair. Results demonstrate that auditory objects generated by temporal proximity are treated as relatively encapsulated units and that automatic deviance-detection may rely on multiple hierarchically organized representations of sound sequences.     

Central Auditory Processing of Durational Changes in Complex Speech Patterns by Newborns: An Event-Related Brain Potential Study

In this study, newborns' ability to discriminate durational changes in the fricative /s/ within a nonsense word was investigated. The results showed that infrequent increments and decrements of a speech sound duration elicit a mismatch negativity kind of response in sleeping human newborns. In the auditory event-related potential to these deviant stimuli two negative waves of this response were revealed. The first negative wave peaked at about 150 msec and the second at about 350 msec after the change onset. At least one negative deflection, which was interpreted as evidence for stimulus change-detection, was observed in every infant.     

Teasing out those age‐related MMPI norms: A response to Lezak

In this study, newborns' ability to discriminate durational changes in the fricative /s/ within a nonsense word was investigated. The results showed that infrequent increments and decrements of a speech sound duration elicit a mismatch negativity kind of response in sleeping human newborns. In the auditory event-related potential to these deviant stimuli two negative waves of this response were revealed. The first negative wave peaked at about 150 msec and the second at about 350 msec after the change onset. At least one negative deflection, which was interpreted as evidence for stimulus change-detection, was observed in every infant.     

The Effects of Indomethacin Administration During Pregnancy on Womens' and Newborns' T-Suppressor Lymphocyte Activity and on HLA Class II Expression by Newborns' Leukocytes

ABSTRACT: It has been previously shown that T lymphocytes from human newborns and pregnant women exert a suppressive activity when assayed on the PWM-induced B cell maturation. The mechanisms of the suppression have remained entirely unknown. Prostaglandin E₂, known to trigger T-cell mediated suppressive activity, may be involved. We took advantage of the treatment of pregnant women with indomethacin, because of premature labor or hydramnios, to investigate the role of prostaglandins in the activation of T suppressor (TS) activity. Administration of indomethacin (250 mg/day for 1–7 weeks, then 150 mg/day for 3–12 weeks) during the third trimester of pregnancy, abrogated the TS activity in the nine women and the three newborns tested. Abrogation of TS activity by indomethacin therapy led to normal PWM-induced B cell maturation in pregnant women but not in newborns. Moreover, the low expression of HLA class II antigens observed on normal newborn B lymphocytes and monocytes was corrected in newborns from indomethacin-treated mothers. Our results strongly suggest that prostaglandins may play a role in induction of TS activity observed in normal pregnant women and newborns and in the decreased expression of HLA class II antigens on newborns' leucocytes. Both phenomena could play a role in immunological interactions between mother and fetus.     

Neurodynamic Studies on Emotional and Inverted Faces in an Oddball Paradigm

The detection of a change in a face stimulus was studied in an oddball paradigm. Event-related potentials (ERPs) and MEG responses to face stimuli were recorded in four conditions: 1) happy standard, neutral deviant; 2) neutral standard, neutral deviant; 3) inverted happy standard, inverted neutral deviant; 4) inverted neutral standard, inverted neutral deviant. In all conditions, the target was a face with glasses. Neutral deviants elicited a negative deflection (with a maximum around 280 ms) in ERP and MEG responses, an effect similar to auditory mismatch negativity. Face inversion diminished deviance-related negativity, implying an important role of face recognition in the observed effect. Emotional content and larger physical differences between stimuli in conditions 1 and 3 compared to conditions 2 and 4 did not show statistically significant effect on the neutral-deviant-related negativity.     

The combined perception of emotion from voice and face: early interaction revealed by human electric brain responses

Judgement of the emotional tone of a spoken utterance is influenced by a simultaneously presented face expression. The time course of this integration was investigated by measuring the mismatch negativity (MMN). In one condition, the standard stimulus was an angry voice fragment combined with a (congruous) angry face expression. In the deviant pair, the voice expression was kept the same and only the face expression changed to an (incongruous) sad face. The pairs with a deviant visual item evoked a negative electric brain response showing the characteristics of the MMN, which is usually evoked only by auditory deviations. Similar results were obtained by employing incongruous standard and congruous deviant pairs. These findings provide compelling evidence of an early integration of face with voice information in the processing of affect.     

N1 response attenuation and the mismatch negativity (MMN) to within‐ and across‐category phonetic contrasts

According to the neural adaptation model of the mismatch negativity (MMN), the sensitivity of this event‐related response to both acoustic and categorical information in speech sounds can be accounted for by assuming that (a) the degree of overlapping between neural representations of two sounds depends on both the acoustic difference between them and whether or not they belong to distinct phonetic categories, and (b) a release from stimulus‐specific adaptation causes an enhanced N1 obligatory response to infrequent deviant stimuli. On the basis of this view, we tested in Experiment 1 whether the N1 response to the second sound of a pair (S₂) would be more attenuated in pairs of identical vowels compared with pairs of different vowels, and in pairs of exemplars of the same vowel category compared with pairs of exemplars of different categories. The psychoacoustic distance between S₁ and S₂ was the same for all within‐category and across‐category pairs. While N1 amplitudes decreased markedly from S₁ to S₂, responses to S₂ were quite similar across pair types, indicating that the attenuation effect in such conditions is not stimulus specific. In Experiment 2, a pronounced MMN was elicited by a deviant vowel sound in an across‐category oddball sequence, but not when the exact same deviant vowel was presented in a within‐category oddball sequence. This adds evidence that MMN reflects categorical phonetic processing. Taken together, the results suggest that different neural processes underlie the attenuation of the N1 response to S₂ and the MMN to vowels.     

Association of CD40 ligand expression on HTLV-I-infected T cells and maturation of dendritic cells

Human T lymphotropic virus type I (HTLV-I) induces HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia (ATL). The development of HAM/TSP is associated with rapid maturation of dendritic cells (DCs), while ATL is accomplished with their maturation defect. The DC maturation is induced by cell-to-cell contact with CD4+ T cells expressing CD40 ligand (L). We determined the influence of CD40L expressed on various HTLV-I-infected T cells on the DC maturation. Around 60% of CD4+ T cells infected with HTLV-I for 1 week, expressed CD40L molecules involved in DC maturation. DCs matured by the CD40L+ T cells activated autologous CD4+ and CD8+ T cells. HTLV-I-immortalized T-cell lines established from healthy donors consistently expressed CD40L molecules for 3 months, however, some lines lost the expression soon thereafter. Interleukin (IL)-2-independent and transformed lines lacked that expression. Furthermore, T cells obtained from HAM/TSP patients expressed CD40L molecules for at least 3 weeks, whereas T cells from ATL patients did not express that. The CD40L T cells did not induce DC maturation, and required exogenous CD40L molecules for maturation. The CD40L+ T-cell-induced maturation was blocked by anti-CD40L antibody. Therefore, the lack of CD40L expression on HTLV-I-infected T cells may be associated with the development of ATL.     

Diagnostic value of CD45RO expression on circulating T lymphocytes of fetuses and newborn infants with pre-, peri- or early post-natal infections

We examined the expression of the CD45RO antigen, which characterizes the antigen primed/memory phenotype of T lymphocytes, as a marker for congenital infection in blood samples of newborns and fetuses. CD45RO expression on T cells was determined by triple-colour fluorescence flow cytometry. In total 537 blood samples of newborns and infants up to an age of 3 months and 89 fetal blood samples from gestational weeks 19–31 were analysed. Of the newborns and infants, 74 had a clinically, serologically and/or antigenically evident infection, and four of the fetuses had a confirmed intra-uterine infection. In 35 infants with acute predominantly bacterial infections such as sepsis or pneumonia, 17 (48.6%) had elevated CD45RO^bright expression. In 39 infants with proven pre-, peri- or early post-natal infections with toxoplasmosis, cytomegalovirus (CMV), rubella, herpes simplex virus (HSV) or human herpes virus type 6 (HHV6), 25 (64.1%) exhibited enhanced CD45RO^bright expression. Three of four fetuses with confirmed intra-uterine infection (three with CMV, one with parvovirus B19) exhibited elevated CD45RO^bright expression. The specificity of the CD45RO assay for detecting microbial infections was 94.6% for newborns and infants up to 3 months and 90.6% for fetuses. It is concluded that elevated numbers of CD45RO^bright T cells in infants up to 3 months of age strongly suggest an infection. However, the sensitivity of the CD45RO assay is not sufficient to enable the test to be used as a general marker for prescreening infants to detect pre-, peri- or early post-natally acquired infections.     

Experimental neonatal syphilis in a susceptible (C4D) and a resistant (Albany) strain of guinea pig.

Despite similar levels of natural antibodies and treponemicidal activity, 83% of fourth complement component-deficient (C4D) mother guinea pigs developed ulcerative lesions to a challenge of 5 x 10(7) Treponema pallidum, whereas 75% of offspring 1 to 5 days old were temporarily (2-3 months) resistant to development of dermal lesions. In contrast, only 17% of Albany-strain mothers developed small papular lesions, while 68% of 1- to 5-day-old newborns developed large papular or ulcerative lesions within 9-15 days postinfection. These findings, together with the late development of both dermal lesions and antibodies in C4D neonates, preclude the concept of an antibody-associated natural resistance. T. pallidum infection in either C4D or Albany neonates was not associated with depletion of any particular cell population in lymphoid tissue. However, marked age- and strain-dependent histologic differences were noted. Histologic examination of lymph nodes and spleens from 17-day-old and 3- to 4-month-old animals showed that maturation of lymphoid tissues in C4D animals lagged behind the Albany strain at either age. Moreover, 75% of C4D newborns contained significantly higher levels of immunomodulatory alpha 1 fetoprotein than Albany neonates. The possibility that differences in susceptibility to T. pallidum infection between C4D and Albany guinea pigs as neonates and again as adults is the result of genetically associated changes in immunologic recognition is discussed.     

Event-Related Potentials and Autonomic Responses to a Change in Unattended Auditory Stimuli

Event-related brain potentials (ERPs) and autonomic nervous system (ANS) responses to occasional pitch and rise-time changes in a task-irrelevant auditory stimulus repeating at short intervals were measured while the subject performed a difficult intellectual task (Raven Matrices). It was found that deviant stimuli elicited the mismatch negativity (MMN) component of the ERP even when they elicited no ANS response. There was no significant difference in the mismatch negativity between trials in which the skin conductance response was or was not elicited. The pitch deviant tone also elicited heart rate deceleration, whereas the rise-time deviant tone tended to elicit a later heart rate acceleration. Neither heart rate change correlated with the mismatch negativity. The pattern of results obtained suggests that the mismatch negativity is generated by an automatic discrimination process associated with the cerebral events initiating the orienting response to stimulus change, but does not necessarily lead to the orienting response elicitation. Longer-latency ERP components tended to show slight covariation with ANS responses. The P3 was larger when a skin conductance response was elicited than when it was not elicited. Further, heart rate change trials tended to be accompanied by larger slow waves than trials with no heart rate response. Heart rate acceleration trials were accompanied by a larger slow parietal positivity and a smaller frontal negativity than were heart rate deceleration trials.     

The effect of stimulus probability on the somatosensory mismatch field

We investigated the effect of deviant stimulus probability on the somatosensory magnetic mismatch negativity (MMNm) using an electrical two-point stimulation. First, we determined the discrimination threshold (DT) of the two-point distance. We applied standard stimuli at a distance that subjects felt as one point and deviant stimuli at a distance that subjects definitely felt as two points. We used three deviant stimulus probabilities, 10, 30, and 50%. The components peaking around 30–70 ms (first component) and 150–250 ms (fourth component) following deviant stimuli were significantly larger than those following standard stimuli in 10% condition, but not in 30 or 50% condition. The equivalent current dipole (ECD) was located in the contralateral primary somatosensory cortex (cSI) for the first component, and in the cSI and in the contralateral secondary somatosensory cortex (cSII) for the fourth component. The peak amplitude of the MMNm decreased as the probability of the deviant stimulus increased. The Somatosensory MMNm was affected by deviant stimulus probability similar to an auditory mismatch negativity (MMN).     

Mechanisms of Generation of Mismatch Negativity and Their Role in the Recognition of Brief Auditory Stimuli

The endogenous components of auditory evoked potentials were studied in the human brain, arising in conditions of voluntary and involuntary attention. Variation of the duration of acoustic stimuli led to a situation in which the generation of mismatch negativity was blocked. The recognition of acoustic stimuli was compared in conditions in which passive perception of the deviant signal in some cases evoked mismatch negativity and in others did not. This demonstrated the following: 1) stimuli not evoking mismatch negativity in the classical oddball paradigm can be recognized efficiently; 2) recognition of stimuli evoking mismatch negativity (in conditions of passive perception) occurs with a significantly shorter response time. The difference in the present experiments was 49–51 msec. There was also an increase in the proportion of correct responses to the deviant stimulus (to 92%). Thus, if the experimental conditions allow the mechanism generating mismatch negativity to trigger, then the response time to the actively perceived stimulus decreases. These results are evidence that the mechanisms of involuntary attention contribute to the active perception of acoustic stimuli.     

Alterations in thymopoiesis in intact and peripubertally orchidectomized adult rats of different age.

In adult rats 3, 6 and 9 months post-orchidectomy performed at the age of 30 days the thymus weight, thymocyte yield and relative proportions of thymocyte subsets (delineated by expression of CD4/CD8 molecules and TCRalphabeta) were analyzed in order to elucidate a putative role of male gonadal hormones in the shaping of thymus size and intrathymic T cell maturation. In 4-month-old control rats the thymus size and cellularity returned to the corresponding levels in 1-month-old rats. These levels were sustained during the following 6 months. In spite of that, the distribution of the main thymocyte subsets in these rats was subjected to significant changes, probably due to an age-associated diminishing thymus ability to provide efficient T cell differentiation. The results added further weight to a potential feedback regulatory role of CD4+8- cells in thymopoiesis. Furthermore, they revealed that the orchidectomy-induced (i) enlargement of the thymus size and enrichment of the thymic lymphoid cell content are of a limited duration; and (ii) alterations in the relative proportion of thymocytes become quantitatively more pronounced with duration of the gonadal deprivation. Thus, the study also indicates that the age-associated changes in gonadal hormones may be, at least partly, responsible for the age-related reshaping of the T cell maturation sequence, and hence for remodeling T cell dependent immune functions.