Central auditory processing in patients with auditory hallucinations

OBJECTIVE: Data from a full assessment of auditory perception in patients with schizophrenia were used to investigate whether auditory hallucinations are associated with abnormality of central auditory processing. METHOD: Three groups of subjects participated in auditory assessments: 22 patients with psychosis and a recent history of auditory hallucinations, 16 patients with psychosis but no history of auditory hallucinations, and 22 normal subjects. Nine auditory assessments, including auditory brainstem response, monotic and dichotic speech perception tests, and nonspeech perceptual tests, were performed. Statistical analyses for group differences were performed using analysis of variance and Kruskal-Wallis tests. The results of individual patients with test scores in the severely abnormal range (more than three standard deviations from the mean for the normal subjects) were examined for patterns that suggested sites of dysfunction in the central auditory system. RESULTS: The results showed significant individual variability among the subjects in both patient groups. There were no group differences on tests that are sensitive to low brainstem function. Both patient groups performed poorly in tests that are sensitive to cortical or high brainstem function, and hallucinating patients differed from nonhallucinating patients in scores on tests of filtered speech perception and response bias patterns on dichotic speech tests. Six patients in the hallucinating group had scores in the severely abnormal range on more than one test. CONCLUSIONS: Hallucinations may be associated with auditory dysfunction in the right hemisphere or in the interhemispheric pathways. However, comparison of results for the patient groups suggests that the deficits seen in hallucinating patients may represent a greater degree of the same types of deficits seen in nonhallucinating patients.     

Transplantation of conditionally immortal auditory neuroblasts to the auditory nerve

Cell transplantation is a realistic potential therapy for replacement of auditory sensory neurons and could benefit patients with cochlear implants or acoustic neuropathies. The procedure involves many experimental variables, including the nature and conditioning of donor cells, surgical technique and degree of degeneration in the host tissue. It is essential to control these variables in order to develop cell transplantation techniques effectively. We have characterized a conditionally immortal, mouse cell line suitable for transplantation to the auditory nerve. Structural and physiological markers defined the cells as early auditory neuroblasts that lacked neuronal, voltage-gated sodium or calcium currents and had an undifferentiated morphology. When transplanted into the auditory nerves of rats in vivo, the cells migrated peripherally and centrally and aggregated to form coherent, ectopic 'ganglia'. After 7 days they expressed beta 3-tubulin and adopted a similar morphology to native spiral ganglion neurons. They also developed bipolar projections aligned with the host nerves. There was no evidence for uncontrolled proliferation in vivo and cells survived for at least 63 days. If cells were transplanted with the appropriate surgical technique then the auditory brainstem responses were preserved. We have shown that immortal cell lines can potentially be used in the mammalian ear, that it is possible to differentiate significant numbers of cells within the auditory nerve tract and that surgery and cell injection can be achieved with no damage to the cochlea and with minimal degradation of the auditory brainstem response.     

Human auditory cortex is activated by omissions of auditory stimuli

Cortical signals associated with infrequent tone omissions were recorded from 9 healthy adults with a whole-head 122-channel neuromagnetometer. The stimulus sequence consisted of monaural (left or right) 50-ms 1-kHz tones repeated every 0.2 or 0.5 s, with 7% of the tones randomly omitted. Tones elicited typical responses in the supratemporal auditory cortices. Omissions evoked strong responses over temporal and frontal areas, independently of the side of stimulation, with peak amplitudes at 145–195 ms. Response amplitudes were 60% weaker when the subject was not attending to the stimuli. Omission responses originated in supratemporal auditory cortices bilaterally, indicating that auditory cortex plays an important role in the brain's modelling of temporal characteristics of the auditory environment. Additional activity was observed in the posterolateral frontal cortex and in the superior temporal sulcus, more often in the right than in the left hemisphere.     

Modified activity of the human auditory cortex during auditory hallucinations.

Previous reports have shown abnormalities in brain metabolism and evoked responses of schizophrenic patients with hallucinations. The authors recorded electric and magnetic auditory responses during transitory auditory hallucinations in two patients. Small but replicable response delays occurred during hallucinations. The results suggest that the effect of hallucinations on auditory cortex activity is similar to the effect of real sounds.     

Comparison of auditory deficits associated with neglect and auditory cortex lesions

In contrast to lesions of the visual and somatosensory cortex, lesions of the auditory cortex are not associated with self-evident contralesional deficits. Only when two or more stimuli are presented simultaneously to the left and right, contralesional extinction has been observed after unilateral lesions of the auditory cortex. Because auditory extinction is also considered a sign of neglect, clinical separation of auditory neglect from deficits caused by lesions of the auditory cortex is challenging. Here, we directly compared a number of tests previously used for either auditory-cortex lesions or neglect in 29 controls and 27 patients suffering from unilateral auditory-cortex lesions, neglect, or both. The results showed that a dichotic-speech test revealed similar amounts of extinction for both auditory cortex lesions and neglect. Similar results were obtained for words lateralized by inter-aural time differences. Consistent extinction after auditory cortex lesions was also observed in a dichotic detection task. Neglect patients showed more general problems with target detection but no consistent extinction in the dichotic detection task. In contrast, auditory lateralization perception was biased toward the right in neglect but showed considerably less disruption by auditory cortex lesions. Lateralization of auditory-evoked magnetic fields in auditory cortex was highly correlated with extinction in the dichotic target-detection task. Moreover, activity in the right primary auditory cortex was somewhat reduced in neglect patients. The results confirm that auditory extinction is observed with lesions of the auditory cortex and auditory neglect. A distinction can nevertheless be made with dichotic target-detection tasks, auditory-lateralization perception, and magnetoencephalography.     

A case of auditory agnosia with the lesion of bilateral auditory radiation

A 53-year-old man showed central auditory disturbance with recurrent cerebral hemorrhage. At his acute stage he had deafness and auditory anosognosia. Two or three months later, there was no deafness and auditory anosognosia, but he could not comprehend words, environmental sounds and music. Auditory brainstem responses showed no peripheral or brainstem damage, and the lesion of bilateral auditory radiation was detected by MRI. His auditory agnosia did not improve over one and a half year. There is no report like such permanent auditory agnosia with the lesion of bilateral subcortical temporal lobe.     

The cognitive neuropsychology of auditory hallucinations: a parallel auditory pathways framework

Auditory hallucinations are generally defined as false perceptions. Recent developments in auditory neuroscience have rapidly increased our understanding of normal auditory perception revealing (partially) separate pathways for the identification ("what") and localization ("where") of auditory objects. The current review offers a reexamination of the nature of auditory hallucinations in schizophrenia using this object-based framework. First, the structural and functional organization of auditory what and where pathways is briefly described. Then, using recent functional neuroimaging data from healthy subjects and patients with schizophrenia, key phenomenological features of hallucinations are linked to abnormal processing both within and between these pathways. Finally, current cognitive explanations of hallucinations, based on intrusive cognitions and impaired source memory, are briefly outlined and set within this framework to provide an integrated cognitive neuropsychological model of auditory hallucinations.     

Brainstem auditory hallucinosis

We studied three patients with findings suggesting that auditory hallucinations may occur with lesions of the tegmentum of the pons and lower midbrain. The evidence was clinical (indicating location of the lesion), radiologic (CT), pathologic in one case, and physiologic (affirming integrity of the cochleas and auditory nerves). The condition is comparable with the Lhermitte peduncular-diencephalic visual hallucinosis.     

The auditory pathology of brain death as revealed by auditory evoked potentials

A case of brain death is reported in which the auditory brainstem response, middle latency component, and slow vertex response were recorded before and after the cessation of cortical activity, and in which histological examination of the temporal bone and central auditory pathways was performed post mortem. Brain death of at least 48 hours' duration was demonstrated by neurological examination, flat electroencephalographic recording, and persistent absence of auditory evoked responses. The postmortem examination was performed 3 hours after death. The pathological studies of the whole length of the auditory pathway revealed total autolysis of the organ of Corti, marked cell loss in the dorsal cochlear nucleus, and moderate cell loss in other nuclei of the central auditory pathway. It should be considered that total autolysis of the organ of Corti and severe cell loss of the cochlear nucleus may occur if the auditory brainstem response becomes absent in comatose patients.     

Functional anatomy of auditory verbal imagery in schizophrenic patients with auditory hallucinations

OBJECTIVE: This study investigated the functional neuroanatomy of inner speech and auditory verbal imagery in schizophrenic patients predisposed to auditory hallucinations. METHOD: Eight patients with schizophrenia with a history of prominent auditory hallucinations and six comparison subjects underwent functional magnetic resonance imaging while generating inner speech or imagining external speech. RESULTS: Patients showed no differences while generating inner speech but experienced a relatively attenuated response in the posterior cerebellar cortex, hippocampi, and lenticular nuclei bilaterally and the right thalamus, middle and superior temporal cortex, and left nucleus accumbens during auditory verbal imagery. CONCLUSIONS: Patients with schizophrenia who were prone to auditory hallucinations show attenuated activation when processing inner speech in areas implicated in verbal self-monitoring.     

Pleasurable auditory hallucinations

OBJECTIVE: The focus in auditory hallucination (AH) research is usually on the negative impact of the experience itself. There are practically no studies on whether voices can be perceived as pleasurable. The aim of the present study was to assess the frequency of voices as a pleasurable experience in a psychotic patient population. METHOD: A total of 160 patients with AHs (89 schizophrenia and 17 other psychoses) were assessed with the psychotic symptom rating scale (PSYRATS) for AHs, including an added item on whether the experience was pleasurable. RESULTS: Twenty-eight patients (26%) reported the voices as a pleasurable experience and 10 of them did so frequently. Pleasurable hallucinations showed negative associations with amount and intensity of distress, degree of negative content and loudness. Positive associations were apparent with chronicity and perceived control over the voices. CONCLUSION: Pleasurable hallucinations can be detected in a substantial proportion of patients, and cross validated with existing instruments.     

Event-related potentials during auditory oddball, and combined auditory oddball-visual paradigms

The purpose of the current study was to investigate the properties of a new modification of the classical auditory oddball paradigm (auditory oddball paradigm combined with passive visual stimulation, AERPs + VEPs) and compare the scalp topography obtained with the new paradigm and the classical auditory oddball paradigm (AERPs) in healthy humans. The responses to bimodal stimulation, and to the classical oddball paradigm were similar to those reported in other studies in terms of location, amplitudes, and latencies of P1, N1, P2, N2, and P300. The new modification of the oddball paradigm produced P300 at fronto-central locations in contrast to centro-parietal locations during the classical oddball paradigm. The amplitudes and latencies of P300 were also significantly larger during the new than the classical paradigm. Furthermore, the amplitudes of N1 and P2, but not N2 were significantly higher and differed in location during the new paradigm in response to both target and standard stimuli. The latencies of all three waves were significantly longer and the latency of P2 differed in location between the new and the classical paradigms in response to only the standard stimuli. The results of this study suggest that the new modification of the classical oddball paradigm produces different neural responses to the classical oddball paradigm. Therefore, this modification can be used to investigate dysfunctions in sensory and cognitive processing in clinical samples.     

Optimized auditory transcranial alternating current stimulation improves individual auditory temporal resolution

Background

Temporal resolution of cortical, auditory processing mechanisms is suggested to be linked to peak frequency of neuronal gamma oscillations in auditory cortex areas (individual gamma frequency, IGF): Individuals with higher IGF tend to have better temporal resolution.

Differential responses of primary auditory cortex in autistic spectrum disorder with auditory hypersensitivity

The aim of this study was to investigate the differential responses of the primary auditory cortex to auditory stimuli in autistic spectrum disorder with or without auditory hypersensitivity. Auditory-evoked field values were obtained from 18 boys (nine with and nine without auditory hypersensitivity) with autistic spectrum disorder and 12 age-matched controls. Autistic disorder with hypersensitivity showed significantly more delayed M50/M100 peak latencies than autistic disorder without hypersensitivity or the control. M50 dipole moments in the hypersensitivity group were larger than those in the other two groups [corrected]. M50/M100 peak latencies were correlated with the severity of auditory hypersensitivity; furthermore, severe hypersensitivity induced more behavioral problems. This study indicates auditory hypersensitivity in autistic spectrum disorder as a characteristic response of the primary auditory cortex, possibly resulting from neurological immaturity or functional abnormalities in it.     

Spatiotemporal differentiation in auditory and motor regions during auditory phoneme discrimination

Auditory phoneme discrimination (APD) is supported by both auditory and motor regions through a sensorimotor interface embedded in a fronto-temporo-parietal cortical network. However, the specific spatiotemporal organization of this network during APD with respect to different types of phonemic contrasts is still unclear. Here, we use source reconstruction, applied to event-related potentials in a group of 47 participants, to uncover a potential spatiotemporal differentiation in these brain regions during a passive and active APD task with respect to place of articulation (PoA), voicing and manner of articulation (MoA). Results demonstrate that in an early stage (50–110 ms), auditory, motor and sensorimotor regions elicit more activation during the passive and active APD task with MoA and active APD task with voicing compared to PoA. In a later stage (130–175 ms), the same auditory and motor regions elicit more activation during the APD task with PoA compared to MoA and voicing, yet only in the active condition, implying important timing differences. Degree of attention influences a frontal network during the APD task with PoA, whereas auditory regions are more affected during the APD task with MoA and voicing. Based on these findings, it can be carefully suggested that APD is supported by the integration of early activation of auditory-acoustic properties in superior temporal regions, more perpetuated for MoA and voicing, and later auditory-to-motor integration in sensorimotor areas, more perpetuated for PoA.