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Lithium alters measures of auditory gating in two strains of mice.

BACKGROUND: There are similarities between schizophrenia and bipolar disorder, especially during the psychotic phase. Auditory gating deficits are common in both schizophrenia (does not remit postpsychotic event) and bipolar disorder (only during the manic phase). Lithium has been used to treat psychosis acutely in both bipolar disorder and schizophrenia. An animal model was used to assess the effects of lithium treatment on normal and deficient auditory gating. METHODS: Mice of the DBA/2 (deficient gating) and C3H (normal gating) strains were treated for 6 weeks with either standard rodent chow or rodent chow supplemented with 2.55g/kg lithium carbonate. After 6 weeks of treatment, auditory evoked potentials were recorded under anesthesia. Differences between the groups and treatments were determined using analysis of variance. RESULTS: The normally impaired DBA/2 mice showed improved auditory gating following lithium treatment, while the C3H mice, the benchmark "normal" mouse strain, were impaired after lithium treatment. CONCLUSIONS: C3H mice treated with lithium had significantly impaired auditory gating as a result of treatment. This may be due to norepinephrine facilitation, through a blockade of presynaptic alpha(2) autoreceptors. DBA/2 mice had improved gating as a result of treatment with lithium, likely due to improved functioning of the gamma-aminobutyric acid system.

Animals↗

Tropisetron improves deficient inhibitory auditory processing in DBA/2 mice: role of alpha 7 nicotinic acetylcholine receptors.

RATIONALE: Deficient inhibitory processing of the P50 auditory evoked potential is a pathophysiological feature of schizophrenia. Several lines of evidence suggest that alpha 7 nicotinic receptors play a critical role in this phenomenon. Similar to schizophrenic patients, DBA/2 mice spontaneously exhibit a deficit in inhibitory processing of the P20-N40 auditory evoked potential, which is thought to be a rodent analog of the human P50 auditory evoked potential. OBJECTIVE: The present study was undertaken to examine whether tropisetron, a partial agonist at alpha 7 nicotinic receptors and an antagonist at 5-hydroxytryptamine-3 receptors, improves this deficit in DBA/2 mice. RESULTS: Administration of tropisetron (1 mg/kg i.p.) significantly improved the deficient inhibitory processing of the P20-N40 auditory evoked potential in DBA/2 mice. Coadministration of methyllycaconitine (MLA; 3 mg/kg i.p.), a partially selective antagonist at alpha 7 nicotinic receptors, significantly blocked the normalizing effect of tropisetron. Furthermore, MLA alone did not alter the deficient inhibitory processing of the P20-N40 auditory evoked potential in DBA/2 mice. CONCLUSIONS: The data suggest that tropisetron improves the deficient inhibitory processing of the P20-N40 auditory evoked potential in DBA/2 mice by effects on alpha 7 and perhaps alpha 4 beta 2 nicotinic receptors. Tropisetron may be useful for the treatment of deficient inhibitory processing in schizophrenia.

Aconitine↗

Psychoacoustical deficits related to bilateral subcortical hemorrhages. A case with apperceptive auditory agnosia.

We report a case of acute deafness secondary to bilateral hemorrhages involving the external capsule and extending to both temporal isthmi. The lesions probably disrupted both auditory radiations. Deafness disappeared within 2 weeks leading to a transient auditory agnosia for environmental and verbal sounds. Performance on audiological and neurolinguistic tests were consistent with the hypothesis of a deficit of non-specific auditory processes. Psychoacoustical deficits related to subcortical lesions are very rare and might differ from those due to cortical lesions by the lack of aphasia. The present case and both previous cases with subcortical lesions might suffer from auditory agnosia of apperceptive type. Its characteristics and the role of non-specific auditory processes are discussed using the data obtained from this third case.

Agnosia↗

Magnetoencephalographic evidence of abnormal auditory processing in amyotrophic lateral sclerosis with bulbar signs.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron damage that gives rise to muscle denervation. Besides motor neuron damage, conscious auditory processing appears to be impaired in ALS, whereas it has remained ambiguous whether preceding automatic auditory processing is abnormal in ALS and specifically in ALS with bulbar signs. METHODS: Auditory evoked fields (AEFs) to monaurally presented frequent and infrequent tones with stimulus intervals of 500 and 2500 ms were recorded with magnetoencephalography (MEG) from 10 ALS patients having bulbar signs and from 10 age-matched healthy subjects. RESULTS: The amplitudes of the P50m and N100m responses, which index automatic auditory processing underlying stimulus detection, were significantly increased and P50m latency was shortened in ALS patients. MMNm, which reflects memory-based auditory comparison process, was increased in amplitude in the patient group, whereas the MMNm latency was similar in both groups. AEF latency and amplitude values failed to correlate with the severity of ALS as measured by ALS Functional Rating Scale (ALSFRS). CONCLUSIONS: The present results suggest that auditory processing underlying stimulus detection, and subsequent memory-based comparison processes are abnormal in ALS patients with severe bulbar signs. This might be due to cortical overactivity of excitatory neurotransmitter glutamate observed in ALS.

Acoustic Stimulation↗

Involuntary attention and distractibility as evaluated with event-related brain potentials.

This article reviews recent event-related brain potential (ERP) studies of involuntary attention and distractibility in response to novelty and change in the acoustic environment. These studies show that the mismatch negativity, N(1) and P(3a) ERP components elicited by deviant or novel sounds in an unattended sequence of repetitive stimuli index different processes along the course to involuntary attention switch to distracting stimuli. These studies used new auditory-auditory and auditory-visual distraction paradigms, which enable one to assess objectively abnormal distractibility in several clinical patient groups, such as those suffering from closed-head injuries or chronic alcoholism.

Attention↗

Event-related potentials and consonant differentiation in newborns with familial risk for dyslexia.

We measured event-related potentials (ERPs) to synthetic consonant-vowel syllables (/ba/, /da/, /ga/) from 26 newborns with familial risk for dyslexia and 23 control infants participating in the Jyväskylä Longitudinal Study of Dyslexia. The syllables were presented with equal probability and with interstimulus intervals ranging from 3,010 to 7,285 ms. Analyses of averaged ERPs from the latencies identified on the basis of principal component analysis (PCA) revealed significant group differences in stop-consonant processing in several latency ranges. At the latencies of 50-170 ms and 540-630 ms, the responses to /ga/ were larger and more positive than those to /ba/ and /da/ in the right hemisphere in the at-risk group. Between 740 and 940 ms, the responses to /ba/ and /da/ differed between anterior and posterior electrode sites in the control group. These results indicate that the cortical electric activation evoked by speech elements differs between children with and without risk for dyslexia even immediately after birth. Group-related effects at early and late latency ranges of ERPs suggest differences both in the early sound processing based on activation of afferent elements and in later phases of syllable encoding.

Auditory Perceptual Disorders↗

[Palinacousis with hemianacusia caused by left temporal lesion].

Palinacousis (auditory perseveration) is reported in a 78-year-old patient with a left temporo parietal astrocytoma. The patient complained of "echoing voice" in his right ear. Palinacousis was associated with sensitive partial seizures. Neuropsychological investigations revealed hemianacusia with normal performance for phonological discrimination and verbal repetition. We suggest that these preserved abilities allowed emergence of palinacousis.

Aged↗

Effects of stimulus-onset asynchrony on the dichotic performance of children with auditory-processing disorders.

Dichotic stop-consonant-vowel identification was investigated in two experiments using two groups of learning-disabled children demonstrating clinical manifestations of auditory-processing disorders, and two groups of matched, control subjects. Two-item, forced-choice paradigms were used in both experiments. Overall (total) dichotic performance for the two learning-disabled groups was significantly lower than that of the control subjects in all dichotic conditions. This lower performance was attributable to the number of trials in which both stimulus items were correctly identified. Analysis of trials in which only one response was correct showed no differences between the groups in terms of magnitude or direction of ear-advantage (right). In conditions where stimulus onsets were separated by 30, 90, and 150 msec, analysis of one-correct trials demonstrated more accurate identification of the temporally lagging stimulus for all subjects. However, as the onset-time separation increased, the control group's identification of leading and lagging items approached equality. The learning-disabled group, on the other hand, showed little increase in identification of temporally leading items even when stimuli were separated by 150 msec. These data suggest learning-disabled children with auditory-processing disorders may have a reduced temporal efficiency in processing rapidly varying acoustic patterns associated with stop-consonants that is observable when speech perceptual mechanisms are stressed through dichotic competition.

Auditory Perceptual Disorders↗

The use of the ADI-R as a diagnostic tool in the differential diagnosis of children with infantile autism and children with a receptive language disorder.

Children with infantile autism and children with a specific receptive language disorder often show similar behavioural problems, making the differentiation between these two diagnostic categories difficult. The purpose of this study is to evaluate the usefulness of parental information in the differential diagnosis of the two types of disorders mentioned above. Sixteen children with a receptive language disorder and 11 children with infantile autism participated in the study. All children had normal non-verbal IQs. The ADI-R (Autism Diagnostic Interview-Revised) was performed with all children. The results showed that the ADI-R items reflecting behavioural features at pre-school age (age range 4-5 years) were better suited to differentiate the groups than the items reflecting behavioural features at the time of the investigation (mean age: 9 years). The items on the dimension "Reciprocal social interaction" and "Communication and language" discriminated the groups better than the items of the dimension "Restricted interests". According to the ICD-10 algorithm of the ADI-R one child with autism and one child with a receptive language disorder were falsely classified. These false classifications were mainly due to a distorted parental perception of the child's behaviour. The ADI-R is a useful tool in the differential diagnosis of developmental disorders.

Algorithms↗

[Mismatch negativity in schizophrenia research. An indicator of early processing disorders of acoustic information].

Mismatch negativity (MMN) represents an event-related component of the auditory evoked potentials at about 100-250 ms, evoked by discernible changes in an ongoing uniform acoustic stimulation. The current paper reviews all recently published MMN studies in the field of schizophrenia research. A reduced MMN in schizophrenic patients is found in the majority of the studies. This deficit is likely to be related to the disorder, since antipsychotic medication seems to have little influence on these results. Interestingly, a reduced MMN is also found in first-degree relatives of patients. Clear evidence for a hemispheric lateralization of the MMN reduction in schizophrenic patients is lacking. A hypofunction of the N-methyl-D-aspartate (NMDA) receptor is discussed as a possible explanation of this deficit.

Auditory Perceptual Disorders↗

Altered performance of schizophrenia patients in an auditory detection and discrimination task: exploring the 'self-monitoring' model of hallucination.

It has been suggested that perceptual hallucination results from a bias in attributing a self-generated event to an external source. The 'self-monitoring' model proposes that the impairment arises from a defective corollary discharge in perceptual decisions. However, psychophysical studies in schizophrenia patients have not found consistent support for the model. We re-explored this issue by including subjects with mood disorders as patient controls and employed signals of variable intensities in an auditory detection and discrimination task. Using signal detection theory, we found decreased sensitivity in auditory detection and discrimination in schizophrenia patients, as compared to control subjects. Moreover, the psychometric functions of schizophrenics had a shallower slope than those of the controls. According to the uncertainty theory of signal detection, this suggested that schizophrenia patients monitored a smaller number of perceptual channels. On the other hand, hallucinating and non-hallucinating schizophrenia patients did not differ from each other, nor did they as a group differ from control subjects in terms of response bias. Overall, our results do not support the idea that hallucination results from an altered bias in the online processing of perceptual signals.

Adult↗

Auditory event-related responses in children with semi-lobar holoprosencephaly.

The purpose of this study was to evaluate auditory sensory and discrimination responses in children with semi-lobar holoprosencephaly (HPE). Event-related potential (ERP) signals were recorded to tone pair stimuli at 62 electrode sites from the scalp using an oddball paradigm (a two-block design, inter-stimulus interval=70 or 300 ms; frequency of tone pair=100 vs. 100 Hz for the frequent and 100 vs. 300 Hz for the infrequent). Latencies and amplitudes of P150, N250, and mismatch negativity (MMN)-like components were compared between children with HPE and controls. Our results revealed less organized ERP waveforms to both stimuli in children with HPE, with diminished P150 and N250 components across brain area. Robust and delayed MMN-like responses were elicited from the children with HPE, with decreased MMN amplitudes in the central, parietal, occipital, and posterior temporal areas. Our results suggest that while brain sensory responses to auditory tones may be impaired in children with semi-lobar HPE, subcomponents of auditory discrimination processes remain functional.

Acoustic Stimulation↗

Neurophysiological evidence for selective auditory attention deficits in children with specific language impairment.

Recent behavioral studies suggest that children with poor language abilities have difficulty with attentional filtering, or noise exclusion. However, as behavioral performance represents the summed activity of multiple stages of processing, the temporal locus of the filtering deficit remains unclear. Here, we used an event-related potential (ERP) paradigm to compare the earliest mechanisms of selective auditory attention in 12 children with specific language impairment (SLI) and 12 matched control children. Participants were cued to attend selectively to one of two simultaneously presented narrative stories. The stories differed in location (left/right speaker), narration voice (male/female), and content. ERPs were recorded to linguistic and nonlinguistic probe stimuli embedded in the attended and unattended story. By 100 ms, typically developing children showed an amplification of the sensorineural response to attended as compared to unattended stimuli. In contrast, children with SLI showed no evidence of sensorineural modulation with attention, despite behavioral performance indicating that they were performing the task as directed. These data are the first to show that SLI children have marked and specific deficits in the neural mechanisms of attention and, further, localize the timing of the attentional deficit to the earliest stages of sensory processing. Deficits in the effects of selective attention on early sensorineural processing may give rise to the diverse set of sensory and linguistic impairments in SLI children.

Acoustic Stimulation↗

The contribution of AERPs (MMN and LDN) to studying temporal vs. linguistic processing deficits in children with reading difficulties.

One of the factors responsible for the appearance of reading problems seems to be a difficulty in discriminating auditory stimuli presented in rapid succession, known as the 'temporal processing hypothesis'. In this study automatic discrimination processes were evaluated in 31 children with reading difficulties and 24 control children between 4 and 8 years of age, using a passive oddball paradigm, in which syllables (/ba/ and /da/) and complex tones were presented. Analysis of the MMN component revealed significant differences between the groups only in the task involving linguistic stimuli, detecting longer latency of the component in the experimental group. The LDN component showed lower amplitudes and delayed latencies in the experimental group during the processing of both types of stimuli. These differences, however, were more marked in the task involving syllables, where a higher mean amplitude was observed in the experimental group than in the control group in the right hemisphere. The task involving complex tones also revealed differences between the groups at the frontal electrodes, indicating different maturative courses of the potential. The findings demonstrate the existence of a strongly pronounced preattentional auditory deficit during phonological processing, and also reveal important differences between the various stages of automatic information processing in children with and without reading disabilities.

Analysis of Variance↗

Impaired detection of variable duration embedded tones in ectopic NZB/BINJ mice.

Utilizing rodent models, prior research has demonstrated a significant association between focal neocortical malformations (i.e. induced microgyria, molecular layer ectopias), which are histologically similar to those observed in human dyslexic brains, and rate-specific auditory processing deficits as seen in language impaired populations. In the current study, we found that ectopic NZB/BINJ mice exhibit significant impairments in detecting a variable duration 5.6 kHz tone embedded in a 10.5 kHz continuous background, using both acoustic reflex modification and auditory event-related potentials (AERP). The current results add further support to the association between focal cortical malformations and impaired auditory processing, and the notion that these auditory effects may occur regardless of the cortical location of the anomaly.

Acoustic Stimulation↗

[Genes of connexin proteins participating in sound perception].

Congenital deafness is a severe, incurable and hardly correctable inherited disease. Mutations in GCB2 and GJB6 genes are most prevalent causes of deafness and occur in patients with hereditary and sporadic deafness all over the world. Some ethnic groups exhibit high rate of heterozygous carriage of most frequent GJB2 mutations (35delG, 167delT, 235delC). Definite association of hereditary deafness and mutational alterations in genes of connexins 26, 30 and 31 shows high informative value of molecular-genetic methods which diagnose hereditary deafness, carriage of mutations in GJB2, GJB3 and GJB6 genes, provide definite probability of the disease in medico-genetic consulting. Further progress in genetics of hereditary hearing loss will raise efficacy of deafness diagnosis at early stages of fetal development and prevent birth of babies with congenital defects of sound perception.

Auditory Perceptual Disorders↗