Profile of auditory information-processing deficits in schizophrenia.
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ABSTRACT:
SUBMITTER: Turetsky BI
PROVIDER: S-EPMC2652872 | biostudies-literature | 2009 Jan
REPOSITORIES: biostudies-literature
Publications
Profile of auditory information-processing deficits in schizophrenia.
Turetsky Bruce I BI Bilker Warren B WB Siegel Steven J SJ Kohler Christian G CG Gur Raquel E RE
Psychiatry research 20081106 1-2
Schizophrenia patients exhibit abnormalities in several different auditory event-related potential (ERP) measures. It is unclear how these abnormalities relate to each other, since multiple measures are rarely acquired from the same sample. This study addressed two related questions: 1) Are specific auditory ERP measures differentially impaired in schizophrenia? 2) Do abnormalities co-aggregate within the same patients? Nine auditory ERP measures were acquired in a single testing session from 23 ...[more]
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Project description:Importance:Neurophysiologic measures of early auditory information processing (EAP) are used as endophenotypes in genomic studies and biomarkers in clinical intervention studies. Research in schizophrenia has established correlations among measures of EAP, cognition, clinical symptoms, and functional outcome. Clarifying these associations by determining the pathways through which deficits in EAP affect functioning would suggest when and where to therapeutically intervene. Objectives:To characterize the pathways from EAP to outcome and to estimate the extent to which enhancement of basic information processing might improve cognition and psychosocial functioning in schizophrenia. Design, Setting, and Participants:Cross-sectional data were analyzed using structural equation modeling to examine the associations among EAP, cognition, negative symptoms, and functional outcome. Participants were recruited from the community at 5 geographically distributed laboratories as part of the Consortium on the Genetics of Schizophrenia 2 from July 1, 2010, through January 31, 2014. This well-characterized cohort of 1415 patients with schizophrenia underwent EAP, cognitive, and thorough clinical and functional assessment. Main Outcome and Measures:Mismatch negativity, P3a, and reorienting negativity were used to measure EAP. Cognition was measured by the Letter Number Span test and scales from the California Verbal Learning Test-Second Edition, the Wechsler Memory Scale-Third Edition, and the Penn Computerized Neurocognitive Battery. Negative symptoms were measured by the Scale for the Assessment of Negative Symptoms. Functional outcome was measured by the Role Functioning Scale. Results:Participants included 1415 unrelated outpatients diagnosed with schizophrenia or schizoaffective disorder (mean [SD] age, 46 [11] years; 979 males [69.2%] and 619 white [43.7%]). Early auditory information processing had a direct effect on cognition (??=?0.37, P?<?.001), cognition had a direct effect on negative symptoms (??=?-0.16, P?<?.001), and both cognition (??=?0.26, P?<?.001) and experiential negative symptoms (??=?-0.75, P?<?.001) had direct effects on functional outcome. The indirect effect of EAP on functional outcome was significant as well (??=?0.14, P?<?.001). Overall, EAP had a fully mediated effect on functional outcome, engaging general rather than modality-specific cognition, with separate pathways that involved or bypassed negative symptoms. Conclusions and Relevance:The data support a model in which EAP deficits lead to poor functional outcome via impaired cognition and increased negative symptoms. Results can be used to help guide mechanistically informed, personalized treatments and support the strategy of using EAP measures as surrogate end points in early-stage procognitive intervention studies.
| S-EPMC5453308 | biostudies-literature
Project description:BackgroundSensory processing abnormalities are common in schizophrenia (SZ) and impact everyday functions, such as speech perception in noisy environments. Auditory-based targeted cognitive training (TCT) is a "bottom up" cognitive remediation intervention designed to enhance the speed and accuracy of low-level auditory information processing. However, the effects of TCT on behavioral measures of central auditory processing (CAP) and the role of CAP function on verbal learning outcomes in SZ are unknown.MethodsSZ (n = 42) and healthy subjects (CTL; n = 18) underwent comprehensive clinical, neurocognitive, and auditory assessments, including tests of hearing sensitivity and speech recognition (Words-in-Noise (WIN), Quick Speech-in-Noise (SIN)). SZ patients were randomized to receive either treatment-as-usual (TAU); or 30-h of TCT + TAU using a stratified, parallel design. SZ patients repeated assessments ~10-12 weeks later.ResultsPatients exhibited deficits in both WIN (p < 0.05, d = 0.50) and SIN (p < 0.01, d = 0.63). A treatment × time interaction on WIN (p < 0.05, d = 0.74), but not SIN discriminability, was seen in the TCT group relative to TAU. Specific enhancements in the 4-dB over background range drove gains in WIN performance. Moreover, SZ patients with greater CAP deficits experienced robust gains in verbal learning after 30-h of TCT relative to SZ patients without CAP impairment (p < 0.01, d = 1.28).ConclusionFindings demonstrate that intensive auditory training enhances the fidelity of auditory processing and perception, such that specific CAP deficits were 'normalized' and were predictive of gains in verbal learning after TCT. It is conceivable that patients with deficiencies in CAP measures may benefit most from TCT and other interventions targeting auditory dysfunction in SZ.
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Project description:BACKGROUND:Only about one third of patients at high risk for psychosis based on current clinical criteria convert to a psychotic disorder within a 2.5-year follow-up period. Targeting clinical high-risk (CHR) individuals for preventive interventions could expose many to unnecessary treatments, underscoring the need to enhance predictive accuracy with nonclinical measures. Candidate measures include event-related potential components with established sensitivity to schizophrenia. Here, we examined the mismatch negativity (MMN) component of the event-related potential elicited automatically by auditory deviance in CHR and early illness schizophrenia (ESZ) patients. We also examined whether MMN predicted subsequent conversion to psychosis in CHR patients. METHODS:Mismatch negativity to auditory deviants (duration, frequency, and duration + frequency double deviant) was assessed in 44 healthy control subjects, 19 ESZ, and 38 CHR patients. Within CHR patients, 15 converters to psychosis were compared with 16 nonconverters with at least 12 months of clinical follow-up. Hierarchical Cox regression examined the ability of MMN to predict time to psychosis onset in CHR patients. RESULTS:Irrespective of deviant type, MMN was significantly reduced in ESZ and CHR patients relative to healthy control subjects and in CHR converters relative to nonconverters. Mismatch negativity did not significantly differentiate ESZ and CHR patients. The duration + frequency double deviant MMN, but not the single deviant MMNs, significantly predicted the time to psychosis onset in CHR patients. CONCLUSIONS:Neurophysiological mechanisms underlying automatic processing of auditory deviance, as reflected by the duration + frequency double deviant MMN, are compromised before psychosis onset and can enhance the prediction of psychosis risk among CHR patients.
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Project description:The extent to which non-linguistic auditory processing deficits may contribute to the phenomenology of primary progressive aphasia is not established. Using non-linguistic stimuli devoid of meaning we assessed three key domains of auditory processing (pitch, timing and timbre) in a consecutive series of 18 patients with primary progressive aphasia (eight with semantic variant, six with non-fluent/agrammatic variant, and four with logopenic variant), as well as 28 age-matched healthy controls. We further examined whether performance on the psychoacoustic tasks in the three domains related to the patients' speech and language and neuropsychological profile. At the group level, patients were significantly impaired in the three domains. Patients had the most marked deficits within the rhythm domain for the processing of short sequences of up to seven tones. Patients with the non-fluent variant showed the most pronounced deficits at the group and the individual level. A subset of patients with the semantic variant were also impaired, though less severely. The patients with the logopenic variant did not show any significant impairments. Significant deficits in the non-fluent and the semantic variant remained after partialling out effects of executive dysfunction. Performance on a subset of the psychoacoustic tests correlated with conventional verbal repetition tests. In sum, a core central auditory impairment exists in primary progressive aphasia for non-linguistic stimuli. While the non-fluent variant is clinically characterized by a motor speech deficit (output problem), perceptual processing of tone sequences is clearly deficient. This may indicate the co-occurrence in the non-fluent variant of a deficit in working memory for auditory objects. Parsimoniously we propose that auditory timing pathways are altered, which are used in common for processing acoustic sequence structure in both speech output and acoustic input.
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Project description:Abnormal brain activity during the processing of simple sounds is evident in individuals with increased genetic liability for schizophrenia; however, the diagnostic specificity of these abnormalities has yet to be fully examined. Because recent evidence suggests that schizophrenia and bipolar disorder may share aspects of genetic etiology the present study was conducted to determine whether individuals with heightened genetic liability for each disorder manifested distinct neural abnormalities during auditory processing. Utilizing a dichotic listening paradigm, we assessed target tone discrimination and electrophysiological responses in schizophrenia patients, first-degree biological relatives of schizophrenia patients, bipolar disorder patients, first-degree biological relatives of bipolar patients and nonpsychiatric control participants. Schizophrenia patients and relatives of schizophrenia patients demonstrated reductions in an early neural response (i.e. N1) suggestive of deficient sensory registration of auditory stimuli. Bipolar patients and relatives of bipolar patients demonstrated no such abnormality. Both schizophrenia and bipolar patients failed to significantly augment N1 amplitude with attention. Schizophrenia patients also failed to show sensitivity of longer-latency neural processes (N2) to stimulus frequency suggesting a disorder specific deficit in stimulus classification. Only schizophrenia patients exhibited reduced target tone discrimination accuracy. Reduced N1 responses reflective of early auditory processing abnormalities are suggestive of a marker of genetic liability for schizophrenia and may serve as an endophenotype for the disorder.
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Project description:Background and Purpose: Auditory processing disorders (APD), tinnitus and hearing loss (HL) are typical issues reported by patients in audiologic clinics. These auditory impairments can be concomitant or mutually excluding. APD are not necessarily accompanied by significant HL, whereas many adults exhibit peripheral HL and typical cognitive deficits often associated with APD. Since HL, tinnitus and APD affects to several parts of the ascending auditory pathway from the periphery to the auditory cortex, there could be some interrelationship between them. For instance, tinnitus has been reported to degrade the auditory localization capacity. Tinnitus is believed to be triggered by deafferentation of normal peripheral input to the central auditory system. This peripheral deficit can be accompanied by HL or not, since a type of permanent cochlear damage (thus deafferentation) without an elevation of hearing thresholds might persist. Therefore, a combined study of APD, tinnitus and HL on the same cohort of patients can be audiologically relevant and worthy. Methods: Statistical analysis is applied to a cohort of 305 patients attending an audiology clinic in Madrid (Spain). This group of patients is first categorized in four subgroups, namely, HLTG (with tinnitus and HL), NHLTG (with tinnitus and without HL), HLNTG (with HL but no tinnitus), and NHLNTG (neither tinnitus nor HL). The statistical variables include Age, Average Auditory Threshold (ATT), for assessing HL, Tinnitus Handicap Inventory (THI), for measuring tinnitus, and a new 25-item Auditory Behavior Questionnaire (ABQ), for scoring APD. Factor analysis is applied to arrange these items into 4 subscales. The internal consistency reliability of this ABQ is confirmed by calculating Cronbach's coefficients α. The test-retest reliability is assessed by the intraclass correlation coefficients, ICC. Statistical techniques applied to the data set include descriptive analysis of variables and Spearman rank correlations (ρ) between them. Results: Overall reliability of ABQ is confirmed by an α value of 0.89 and by an ICC of 0.91. Regarding the internal consistency reliability, the four subscales prove a fairly good consistency with α coefficients above 0.7. Average values of statistical variables show significantly lower age of patients with tinnitus and no HL, which can provide a cue of noise overexposure of this segment of population. These younger patients show also decreased ABQ and similar THI in comparison with patients in the other subgroups. A strong correlation (ρ = 0.63) was found between AAT and Age for the HLNTG subgroup. For the HLTG subgroup, a moderate correlation (ρ = 0.44) was found between ABQ and THI. Conclusion: The utilized questionnaire (ABQ), together with AAT and THI, can help to study comorbid hearing impairments in patients regularly attending an audiological clinic.
| S-EPMC5382167 | biostudies-literature
Project description:BackgroundPeople with schizophrenia (PSZ) have profound deficits in context processing, an executive process that guides adaptive behaviors according to goals and stored contextual information. Although various neural processes are involved in context processing and are affected in PSZ, the core underlying neural dysfunction is unclear.MethodsTo determine the relative importance of neural dysfunctions within prefrontal cognitive control, sensory activity, and motor activity to context processing deficits in PSZ, we examined event-related potentials (ERPs) in 60 PSZ and 51 healthy control subjects during an optimal context processing task. We also analyzed the Ex-Gaussian reaction time distribution to examine abnormalities in motor control variability in PSZ.ResultsCompared with healthy control subjects, PSZ had lower response accuracy and greater variability in their normal reaction times during high context processing demands. Latencies of normal and slow responses were generally increased in PSZ. High context processing-related reductions in frontal ERPs were indicative of specific deficits in proactive and reactive cognitive controls in PSZ, while ERPs associated with visual and motor processes were reduced regardless of context processing demands, indicating generalized visuomotor deficits. In contrast to previous studies, we found that diminished frontal responses reflective of proactive control of the contextual cue, rather than visual responses of cue encoding, predicted response accuracy deficits in PSZ. In addition, probe-related ERP components of motor preparation, prefrontal reactive control, and frontomotor interaction predicted Ex-Gaussian indices of reaction time instability in PSZ.ConclusionsPrefrontal proactive and reactive control deficits associated with failures in using mental representation likely underlie context processing deficits in PSZ.
| S-EPMC6612435 | biostudies-literature