Neural correlates of verbal and nonverbal semantic integration in children with autism spectrum disorders.

BACKGROUND: Autism is a pervasive developmental disorder characterized by deficits in social-emotional, social-communicative, and language skills. Behavioral and neuroimaging studies have found that children with autism spectrum disorders (ASD) evidence abnormalities in semantic processing, with particular difficulties in verbal comprehension. However, it is not known whether these semantic deficits are confined to the verbal domain or represent a more general problem with semantic processing. The focus of the current study was to investigate verbal and meaningful nonverbal semantic processing in high-functioning children with autism (mean age = 5.8 years) using event-related potentials (ERPs). METHOD: ERPs were recorded while children attended to semantically matching and mismatching picture-word and picture-environmental sound pairs. RESULTS: ERPs of typically developing children exhibited evidence of semantic incongruency detection in both the word and environmental sound conditions, as indexed by elicitation of an N400 effect. In contrast, children with ASD showed an N400 effect in the environmental sound condition but not in the word condition. CONCLUSIONS: These results provide evidence for a deficiency in the automatic activation of semantic representations in children with ASD, and suggest that this deficit is somewhat more selective to, or more severe in, the verbal than the nonverbal domain.

Two Patients with Niemann Pick Disease Type C Diagnosed in the Seventh Decade of Life.

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare, autosomal recessive lysosomal lipid storage disorder. It may present with cerebellar ataxia, vertical supranuclear gaze palsy, and cognitive impairment, and the age of symptom onset in adult-onset NPC is usually earlier than the fourth decade. CASES: We present 2 patients with adult-onset NPC diagnosed in the seventh decade of life. The slow motor progression and subtle findings of supranuclear vertical gaze palsy and ataxia can lead to a delayed diagnosis and misdiagnosis with parkinsonian disorders, particularly progressive supranuclear palsy. CONCLUSION: This report highlights and differentiates key clinical characteristics between NPC and parkinsonian disorders. It is important to consider NPC in the differential diagnosis when patients present with slowed vertical saccades, vertical supranuclear gaze palsy, ataxia, and cognitive impairment present at any age. This will allow appropriate and prompt treatment with miglustat and novel experimental therapies.

Resolution of tardive tremor after bilateral subthalamic nucleus deep brain stimulation placement.

BACKGROUND: Tardive tremor (TT) is an underrecognized manifestation of tardive syndrome (TS). In our experience, TT is a rather common manifestation of TS, especially in a setting of treatment with aripiprazole, and is a frequent cause of referrals for the evaluation of idiopathic Parkinson disease. There are reports of successful treatment of tardive orofacial dyskinesia and dystonia with deep brain stimulation (DBS) using globus pallidus interna (GPi) as the primary target, but the literature on subthalamic nucleus (STN) DBS for tardive dyskinesia (TD) is lacking. To the best of our knowledge, there are no reports on DBS treatment of TT. CASE DESCRIPTION: A 75-year-old right-handed female with the medical history of generalized anxiety disorder and major depressive disorder had been treated with thioridazine and citalopram from 1980 till 2010. Around 2008, she developed orolingual dyskinesia. She was started on tetrabenazine in June 2011. She continued to have tremors and developed Parkinsonian gait, both of which worsened overtime. She underwent DBS placement in the left STN in January 2017 with near-complete resolution of her tremors. She underwent right STN implantation in September 2017 with similar improvement in symptoms. CONCLUSION: While DBS-GPi is the preferred treatment in treating oral TD and dystonia, DBS-STN could be considered a safe and effective target in patients with predominating TT and/or tardive Parkinsonism. This patient saw a marked improvement in her symptoms after implantation of DBS electrodes, without significant relapse or recurrence in the years following implantation.

A developmental ERP study of verbal and non-verbal semantic processing.

To clarify how different the processing of verbal information is from the processing of meaningful non-verbal information, the present study characterized the developmental changes in neural responses to words and environmental sounds from pre-adolescence (7-9 years) through adolescence (12-14 years) to adulthood (18-25 years). Children and adults' behavioral and electrophysiological responses (the N400 effect of event-related potentials) were compared during the processing of words and environmental sounds presented in semantically matching and mismatching picture contexts. Behavioral accuracy of picture-sound matching improved until adulthood, while reaction time measures leveled out by age 12. No major electrophysiological changes in the N400 effect were observed between pre-adolescence and adolescence. When compared to adults, children demonstrated significant maturational changes including longer latencies and larger amplitudes of the N400 effect. Interestingly, these developmental differences were driven by stimulus type: the Environmental Sound N400 effect decreased in latency from adolescence to adulthood, while no age effects were observed in response to Words. Thus, while the semantic processing of single words is well established by 7 years of age, the processing of environmental sounds continues to improve throughout development.

Event-related potential features indexing central auditory discrimination by newborns.

Behavioral research has produced little evidence on sound feature discrimination in neonates. Sensory processes underlying sound perception can be studied using the mismatch negativity (MMN) component of auditory event-related potentials (ERPs), which is not contingent on conscious perception and response. Thus, MMN is suitable for studying newborns, who are difficult to obtain behavioral responses from. The present study thus utilized spectrally rich sounds, known to elicit the most replicable MMN in adults, to investigate newborns' preattentive analysis of sound duration and frequency changes. An attempt was also made to control for the obligatory ERP effects on the MMN. Three-partial harmonic tones were presented in Duration and in Frequency oddball conditions to 55 newborns. In the other two, Equiprobable duration and Equiprobable frequency, conditions frequency and duration deviants of the oddball paradigms were presented with equal probabilities among sounds of other durations and frequencies. MMN was elicited in 81% of newborns in Frequency oddball condition and in 78% of newborns in Duration oddball condition. No significant amplitude differences between the duration and frequency MMNs were found, but MMN latency was delayed in Duration condition. The obligatory components seemed to contribute significantly to the deviant-standard difference in Duration but not in Frequency condition. The majority of neonates appear to possess effective sound frequency and duration discrimination mechanisms. Their preattentive sound discrimination is facilitated by spectrally rich sound content. The present findings support a change-detection nature of MMN in neonates; however, sound duration-related obligatory effects need to be taken into account in infant MMN studies.

Maturation of the auditory change detection response in infants: a longitudinal ERP study.

Mismatch negativity (MMN) is a negative component of auditory event-related potential (ERP), reflecting the brain's automatic change detection process. In the present study we investigated the development of the pitch change detection, as indexed by the MMN, in the same infants from birth until 12 months of age. The MMN was identified in approximately 75% of infants at each age, being relatively stable in latency and amplitude at the group level across the ages studied. However, within the same subjects the MMN substantially varied from age to age. The inspection of individual data revealed a possible source of this variability: in a portion of 3- to 9-month-old infants, a large-amplitude positive component commenced at the latency of the MMN and thus might have masked it. The results of the additional experiment, employing distracting novel sounds in 2-year-old infants and newborns, suggested that the observed positive component could represent an infant analogue of the adult P3a response, indexing an involuntary orienting of attention. Therefore, the variability from age to age might be, at least partially, caused by the differences in degree of infants' orienting, resulting in the reduction of the scalp recorded mismatch negativity in recordings when the orienting P3a positivity was elicited.

Maturation of the auditory event-related potentials during the first year of life.

This study examined the maturation of cortical auditory event-related potentials (ERPs) from birth until 12 months of age. In the 15 infants studied, all ERP peaks observable at 12 months of age, the P150, N250, P350, and N450 were identifiable already at birth, As in previous studies, the amplitudes of the ERP peaks increased and latencies shortened with increasing age. In addition, the time courses of the amplitude growth of these peaks differed from each other. It was concluded, that the generators of all the infantile ERP peaks are functional already at birth, and that the maturational changes in the waveform morphology can mostly be accounted for by the changing relative strengths of the different generators.

Maturation of cortical sound processing as indexed by event-related potentials.

OBJECTIVES: Children's auditory event-related potentials (ERPs) are dominated by the P1 and N2 peaks, while the N1 wave emerges between 3 and 4 years of age. The neural substrates and the behavioral correlates of the protracted N1 maturation, as well as of the 10-year long predominance of the N2 are unclear. The present study utilized high-resolution electroencephalography to study the maturation of auditory ERPs from age 4 to adulthood and to compare the sources of the N1 and the N2 peaks in 9-year-old children and adults. METHODS: Three partial harmonic tones were delivered with short (700 ms) and long (mean of 5s) stimulus onset asynchrony (SOA), with only 700 ms SOA used with 4-year-olds. RESULTS: With a short SOA, 4- and 9-year-old children displayed P1 and N2 peaks, whereas adults showed P1, N1, P2, and N2 waves. With a long SOA, 9-year-olds also displayed an N1 peak, which was frontal in scalp distribution to that in adults who showed P1, N1, and P2 peaks. After filtering out the slow N2 activity, the N1 wave was also revealed in the short-SOA data in 9-year-old but not in 4-year-old children. In adults and in 9-year-olds, the neural sources of the N2 and N1 mapped onto the superior aspects of the temporal lobes, the sources of the N2 being anterior to those of the N1. CONCLUSIONS: The results indicated that children's N1 is composed of differently weighted components as that in adults, and that in both children and adults the N1 and N2 are generated by anatomically distinct generators. A protracted ontogeny of the N1 could be linked with that of auditory sensitivity and orienting, whereas the P1 and N2 peaks are suggested to reflect auditory sensory processes.

Event-related potentials associated with second language learning in children.

OBJECTIVE: In this study, we investigated learning-related changes in auditory event-related potentials (ERPs) of Finnish-speaking 3-6-year-old children caused by learning French language. METHODS: Using an oddball paradigm, ERPs to sounds of French language were recorded in the two groups of healthy children: those who were learning French (experimental group) and those who were not learning any foreign language (control peers). RESULTS: When the children from the experimental group were exposed to the foreign language, they automatically developed French-specific memory traces that helped them to discriminate, categorize, and pronounce utterances of the new language as indicated by the mismatch negativity (MMN) component of the ERPs in a previous study. We found that the learning process was also reflected by changes in P3a and late difference negativity (LDN) responses. Unlike MMN and P3a, the LDN has been discovered relatively recently and its functional role remains unclear. Similarly, as the MMN magnitude increased during the learning process, an increase of the P3a (known to reflect the involuntary attention switching toward deviant stimuli) and LDN amplitudes was observed. The ERPs of the control peers did not change significantly over the test period. CONCLUSIONS: When phonemes of a foreign language are learned, this process is accompanied with the increase in the MMN, P3a, and LDN amplitudes in children. Though the functional significance of LDN remains to be further investigated, our results support its possible link to reorienting processes following distraction.

Mismatch negativity shows that 3-6-year-old children can learn to discriminate non-native speech sounds within two months.

Using 3-6-year-old children as subjects, we describe the neural plasticity accompanying the concurrent learning of a foreign language in a natural environment. Children were monitored for 6 months as they either enrolled in schools or daycare centers where only Finnish was spoken (Control group) or as they joined a French school or a daycare center where French was spoken 50-90% of the time (Experimental group). Whereas mismatch negativity (MMN)--a brain's electrical change-detection response--for a French speech contrast was initially absent or very small in both groups, it was conspicuous 2 months after Finnish children had joined a French kindergarten. Consequently, the data suggest that youngsters can learn to distinguish non-native speech sounds in natural language environment without any special training in just a couple of months. Accordingly, these data herald the vast potential MMN may entail for studying language learning, especially in situations where behavioral responses cannot be readily elicited.

Deficient auditory processing in children with Asperger Syndrome, as indexed by event-related potentials.

Asperger Syndrome (AS) is characterized by normal language development but deficient understanding and use of the intonation and prosody of speech. While individuals with AS report difficulties in auditory perception, there are no studies addressing auditory processing at the sensory level. In this study, event-related potentials (ERP) were recorded for syllables and tones in children with AS and in their control counterparts. Children with AS displayed abnormalities in transient sound-feature encoding, as indexed by the obligatory ERPs, and in sound discrimination, as indexed by the mismatch negativity. These deficits were more severe for the tone stimuli than for the syllables. These results indicate that auditory sensory processing is deficient in children with AS, and that these deficits might be implicated in the perceptual problems encountered by children with AS.

Deficient speech-sound processing, as shown by the electrophysiologic brain mismatch negativity response, and naming ability in prematurely born children.

Very low birth weight (VLBW, <1500 g) preterm birth has been associated with anatomic abnormalities in brain development and cognitive and language disorders. We examined object naming ability, and an electrophysiologic index of auditory sensory discrimination of speech sounds (the mismatch negativity, MMN) in 4-year-old VLBW prematurely born children. We found that half of the VLBW children were inferior to their controls in the object naming ability. Also the MMN amplitudes were smaller in the preterm group as compared with the controls. Further, the MMN amplitude varied as a function of children's performance on object naming, such that the weaker object-naming performance of the preterm group was paralleled by the diminished MMN amplitudes. Therefore, difficulties in auditory discrimination seem to be implicated in language difficulties encountered in VLBW prematurely born children.

Electric brain responses obtained from newborn infants to changes in duration in complex harmonic tones.

Event-related brain potentials of 10 full-term newborns in response to duration changes in complex, harmonic tones known to elicit prominent mismatch negativity (MMN) response in adults were investigated. Here we report that duration changes elicited prominent MMN responses in a 11 newborns tested. In contrast, MMN has been reported in as little as 50% of the infants in some previous studies using other sound attributes. When the infant MMN latency was compared with that obtained from adults, and 4- as well as 8-year-old children, it was found that the MMN latency was a bit later in newborns than in older age groups. This result is consistent with previous findings. The MMN amplitude, however, was surprisingly large in infants compared to older children.

Sound complexity and 'speechness' effects on pre-attentive auditory discrimination in children.

The evidence in adults suggests that at a cortical level simple and complex sounds are processed by partly divergent subsystems. In children, central processing of sounds differing in complexity has not been investigated. Therefore, the present study examined preconscious discrimination of the differences in sound frequency and duration as a function of sound complexity in 8-10-year-old children. A mismatch negativity (MMN) component of auditory event-related potentials was elicited in a paradigm where 'deviant' (rare) stimuli were either shorter in duration or higher in frequency than the 'standard' (repetitive) sounds. Vowels and vowel-matched complex and simple tones were presented in separate sequences. The stimulus complexity effects were sizable and appeared as larger areas and shorter and more consistent latencies of the MMNs, elicited by more complex stimuli. In addition, the vowel frequency MMN showed left hemisphere preponderance compared to the complex tone frequency MMN. No such effect was found for the duration decrement MMNs. In addition, the complex tone duration decrement MMN was distributed posteriorly to either the vowel or sinusoidal tone MMNs. A late discriminative negativity, LDN, did not show consistent effects of sound complexity. In conclusion, acoustically rich sound content facilitates auditory sensory discrimination in 8-10-year-old children. The sound 'speechness' effects were not as robust though present. Unlike adults, children demonstrated high intersubject variability in discriminating spectrally poor, but not rich, sounds. The discrimination of the sound duration appears to differ from that of the sound frequency in nature and, consequently, in the neural substrates.

Verbal and nonverbal semantic processing in children with developmental language impairment.

In an effort to clarify whether semantic integration is impaired in verbal and nonverbal auditory domains in children with developmental language impairment (a.k.a., LI and SLI), the present study obtained behavioral and neural responses to words and environmental sounds in children with language impairment and their typically developing age-matched controls (ages 7-15 years). Event-related brain potentials (ERPs) were recorded while children performed a forced-choice matching task on semantically matching and mismatching visual-auditory, picture-word and picture-environmental sound pairs. Behavioral accuracy and reaction time measures were similar for both groups of children, with environmental sounds eliciting more accurate responses than words. In picture-environmental sound trials, behavioral performance and the brain's response to semantic incongruency (i.e., the N400 effect) of the children with language impairment were comparable to those of their typically developing peers. However, in picture-word trials, children with LI tended to be less accurate than their controls and their N400 effect was significantly delayed in latency. Thus, the children with LI demonstrated a semantic integration deficit that was somewhat specific to the verbal domain. The particular finding of a delayed N400 effect is consistent with the storage deficit hypothesis of language impairment (Kail & Leonard, 1986) suggesting weakened and/or less efficient connections within the language networks of children with LI.

Atypical auditory event-related potentials in preterm infants during the first year of life: a possible sign of cognitive dysfunction?

We assessed auditory event-related potentials in small-for-gestational-age (SGA; 850 +/- 258 g, 28.9 +/- 3.3 gestational wk; n = 15) and appropriate for gestational age (AGA; 1014 +/- 231 g, 26.9 +/- 1.9 gestational wk; n = 20) preterm infants and healthy term infants (n = 22). An oddball paradigm was used with a harmonic tone of 500-Hz frequency as the standard and of 750-Hz frequency as the deviant stimulus. The preterm infants were studied at 40 gestational wk and at 6 and 12 mo of corrected age, and the control subjects were studied at 2-4 d and at 3, 6, 9, 12, and 15 mo of age. The peaks of interest were the main positive peak (P350), the negative peaks at 250 ms (N250) and 650 ms (Nc), and the mismatch negativity at 200 ms (MMN). At term, the P350 in the preterm infants was similar to that of the newborn control subjects. In response to the deviant, the Nc was smaller in the SGA than in the AGA (P < 0.02) and control (P < 0.005) infants. The N250 amplitude was also lower in the SGA infants. At 12 mo, the MMN was observed in the control but not in the preterm infants, whose broad difference positivity correlated with the Bayley developmental index. The decreased Nc and N250 peaks in the SGA infants may suggest an increased risk for cognitive dysfunction. The broad difference positivity at 1 y of age may indicate atypical cortical auditory processing. Whether cognitive dysfunction can be predicted by these findings needs to be assessed in a study with extended follow-up.

A case study of amnion rupture sequence with acalvaria, blindness, and clefting: clinical and psychological profiles.

The purpose of this article is to report the case of a 10-year-old girl born with anophthalmia, bilateral oblique facial clefts, and missing scalp and bones over the temporal and parietal areas of the cranial vault bilaterally. Early amnion rupture seems to be the most probable cause of this rare combination of anomalies. Because no similar case has been reported in the literature so far, we describe here the clinical and psychosocial history of this unusual patient, who has been able to live the intellectually and socially normal life of a blind child in spite of the major craniofacial deformities. The already completed and possible future therapeutic strategies are discussed.

Auditory sensory impairment in children with oral clefts as indexed by auditory event-related potentials.

Children with nonsyndromic oral clefts and with the CATCH 22 syndrome (acronym for cardiac defects, abnormal faces, thymus hypoplasia, clefts, and hypocalcemia) display a range of language and learning disabilities, the neurofunctional bases of which are not yet understood. This review summarizes recent event-related brain potential (ERP) studies on central auditory processing in infants and children with different cleft types and presents an effort to integrate these ERP and earlier behavioral findings into a workable hypothesis on the mechanisms of cognitive impairment in the oral cleft population. The encoding of the acoustic sound features and the functioning of auditory sensory memory (ASM) were studied by recording cortical auditory ERPs. Tapped were two ASM functions: tone pitch discrimination and the duration of sensory memory for tone pitch. In infants with cleft palate, tone pitch discrimination was impaired at birth and at 6 months of age. In infants with cleft lip and palate, no ASM impairment was detected at either age. In school-aged children with clefts and CATCH 22 syndrome, the discrimination of tone pitch was intact under optimal stimulation conditions. However, in these children, shortened duration of ASM was observed, with the magnitude of its shortening covarying with cleft type and being most pronounced in children with CATCH 22 syndrome. The different types of ASM dysfunction found in children with different cleft types could not be accounted for by the peripheral hearing deficits. The relation between ASM dysfunction and known behavioral cognitive disability profiles in children with different cleft types suggests that ASM is implicated in language disabilities of children with oral clefts. Furthermore, it appears that the ASM impairment and oral clefting are linked in a comorbid fashion.

The auditory sensory memory trace decays rapidly in newborns.

The present study investigated the temporal dynamics of auditory sensory memory in newborns as reflected by the mismatch negativity (MMN), a preattentive electric change-detection response. MMN was obtained from 24 full-term healthy newborns who were either awake or asleep (quiet or active sleep) during the experiments. Stimuli were 1,000 Hz tones (standards) that were occasionally replaced by 1,100 Hz tones (deviants). The constant stimulus onset asynchrony (SOA) was, in separate blocks, either 450, 800, or 1,500 ms. A prominent MMN was obtained at the 800 ms SOA in all three sleep or waking states, whereas no MMN occurred at 450 and 1,500 ms SOAs. In view of the fact that in adults MMN is elicited even with a 10s SOA, these results imply that the time span of auditory memory is considerably shorter in neonates than in adults and 8-12-year-old children.