The effectiveness of the combined transcranial direct current stimulation (tDCS) and tailor-made notched music training (TMNMT) on psychoacoustic, psychometric, and cognitive indices of tinnitus patients.

PURPOSE: Tinnitus network(s) consists of pathways in the auditory cortex, frontal cortex, and the limbic system. The cortical hyperactivity caused by tinnitus may be suppressed by neuromodulation techniques. Due to the lack of definitive treatment for tinnitus and limited usefulness of the individual methods, in this study, a combination of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) and tailor-made notched music training (TMNMT) was used. MATERIAL AND METHODS: In this descriptive-analytic study, 26 patients with chronic unilateral tinnitus of the right ear were randomly divided into the clinical trial group (CTG) and the control group (CG). In both groups, six sessions of tDCS with 2 mA intensity for 20 min, with anode on F4 and cathode on F3, were conducted. Simultaneous with tDCS sessions, and based on TMNMT, the participant was asked to listen passively for 120 min/day, to a CD containing her/his favorite music with a proper notch applied in its spectrum according to the individual's tinnitus The treatment outcome was measured by, psychoacoustic (loudness-matching), psychometric (awareness, loudness and annoyance Visual Analogue Scale (VAS) scores, and Tinnitus Handicap Inventory (THI)) scores, and cognitive assessments (randomized dichotic digits test (RDDT) and dichotic auditory-verbal memory test (DAVMT)). Repeated measurement test was used for statistical analyses. RESULTS: In the CTG, the tinnitus loudness and annoyance VAS scores, and THI were reduced significantly (p = 0.001). In addition, the DAVMT and RDDT scores were enhanced (p = 0.001). Such changes were not observed in the CG (p > 0.05). CONCLUSION: The combination of tDCS and TMNMT led to a reduction in the loudness, awareness, annoyance, and also disability induced by tinnitus in CTG. Furthermore, this method showed an improvement of cognitive functions (auditory divided attention, selective attention and working memory) in the CTG.

Auditory hallucinations activate language and verbal short-term memory, but not auditory, brain regions.

Auditory verbal hallucinations (AVH, 'hearing voices') are an important symptom of schizophrenia but their biological basis is not well understood. One longstanding approach proposes that they are perceptual in nature, specifically that they reflect spontaneous abnormal neuronal activity in the auditory cortex, perhaps with additional 'top down' cognitive influences. Functional imaging studies employing the symptom capture technique-where activity when patients experience AVH is compared to times when they do not-have had mixed findings as to whether the auditory cortex is activated. Here, using a novel variant of the symptom capture technique, we show that the experience of AVH does not induce auditory cortex activation, even while real speech does, something that effectively rules out all theories that propose a perceptual component to AVH. Instead, we find that the experience of AVH activates language regions and/or regions that are engaged during verbal short-term memory.

Dichotic listening deficits in amblyaudia are characterized by aberrant neural oscillations in auditory cortex.

OBJECTIVE: Children diagnosed with auditory processing disorder (APD) show deficits in processing complex sounds that are associated with difficulties in higher-order language, learning, cognitive, and communicative functions. Amblyaudia (AMB) is a subcategory of APD characterized by abnormally large ear asymmetries in dichotic listening tasks. METHODS: Here, we examined frequency-specific neural oscillations and functional connectivity via high-density electroencephalography (EEG) in children with and without AMB during passive listening of nonspeech stimuli. RESULTS: Time-frequency maps of these "brain rhythms" revealed stronger phase-locked beta-gamma (~35 Hz) oscillations in AMB participants within bilateral auditory cortex for sounds presented to the right ear, suggesting a hypersynchronization and imbalance of auditory neural activity. Brain-behavior correlations revealed neural asymmetries in cortical responses predicted the larger than normal right-ear advantage seen in participants with AMB. Additionally, we found weaker functional connectivity in the AMB group from right to left auditory cortex, despite their stronger neural responses overall. CONCLUSION: Our results reveal abnormally large auditory sensory encoding and an imbalance in communication between cerebral hemispheres (ipsi- to -contralateral signaling) in AMB. SIGNIFICANCE: These neurophysiological changes might lead to the functionally poorer behavioral capacity to integrate information between the two ears in children with AMB.

Neural network dynamics underlying gamma synchronization deficits in schizophrenia.

Gamma-band (40-Hz) activity is critical for cortico-cortical transmission and the integration of information across neural networks during sensory and cognitive processing. Patients with schizophrenia show selective reductions in the capacity to support synchronized gamma-band oscillations in response to auditory stimulation presented 40-Hz. Despite widespread application of this 40-Hz auditory steady-state response (ASSR) as a translational electroencephalographic biomarker for therapeutic development for neuropsychiatric disorders, the spatiotemporal dynamics underlying the ASSR have not been fully characterized. In this study, a novel Granger causality analysis was applied to assess the propagation of gamma oscillations in response to 40-Hz steady-state stimulation across cortical sources in schizophrenia patients (n = 426) and healthy comparison subjects (n = 293). Both groups showed multiple ASSR source interactions that were broadly distributed across brain regions. Schizophrenia patients showed distinct, hierarchically sequenced connectivity abnormalities. During the response onset interval, patients exhibited abnormal increased connectivity from the inferior frontal gyrus to the superior temporal gyrus, followed by decreased connectivity from the superior temporal to the middle cingulate gyrus. In the later portion of the ASSR response (300-500 ms), patients showed significantly increased connectivity from the superior temporal to the middle frontal gyrus followed by decreased connectivity from the left superior frontal gyrus to the right superior and middle frontal gyri. These findings highlight both the orchestration of distributed multiple sources in response to simple gamma-frequency stimulation in healthy subjects as well as the patterns of deficits in the generation and maintenance of gamma-band oscillations across the temporo-frontal sources in schizophrenia patients.

Long-term auditory processing outcomes in early implanted young adults with cochlear implants: The mismatch negativity vs. P300 response.

OBJECTIVE: Long-term outcomes of early implanted, young adult cochlear implant (CI) users remain variable. We measured auditory discrimination by means of event-related potentials in this population to examine whether variability at the level of cortical auditory processing helps to explain speech abilities. METHODS: Using an auditory oddball paradigm, the P300 and Mismatch Negativity (MMN) were measured in 8 young adult CI users and 14 normal-hearing peers. We related P300 amplitude and latency to clinical speech perception scores in quiet and to duration of deafness. RESULTS: All individuals showed P300 responses. The MMN response was less robust in both groups. There was no evidence for differences in P300 responses between CI users and controls. P300 amplitude was associated with speech perception scores (r = 0.70, p = .05) and duration of deafness (r = -0.83, p = .009). CONCLUSIONS: Early CI implantation yields good auditory processing outcomes at young adult age and, in contrast to MMN, the P300 provides a robust measure for auditory processing on an individual level. SIGNIFICANCE: At the cortical level, early implanted, long-term CI users have good auditory discrimination, leaving variability in implantation outcomes unexplained. This group provides unique insight into the long-term neurophysiological underpinnings of early implantation.

Attentional modulation of neural entrainment to sound streams in children with and without ADHD.

To extract meaningful information from complex auditory scenes like a noisy playground, rock concert, or classroom, children can direct attention to different sound streams. One means of accomplishing this might be to align neural activity with the temporal structure of a target stream, such as a specific talker or melody. However, this may be more difficult for children with ADHD, who can struggle with accurately perceiving and producing temporal intervals. In this EEG study, we found that school-aged children's attention to one of two temporally-interleaved isochronous tone 'melodies' was linked to an increase in phase-locking at the melody's rate, and a shift in neural phase that aligned the neural responses with the attended tone stream. Children's attention task performance and neural phase alignment with the attended melody were linked to performance on temporal production tasks, suggesting that children with more robust control over motor timing were better able to direct attention to the time points associated with the target melody. Finally, we found that although children with ADHD performed less accurately on the tonal attention task than typically developing children, they showed the same degree of attentional modulation of phase locking and neural phase shifts, suggesting that children with ADHD may have difficulty with attentional engagement rather than attentional selection.

Sexually dimorphic patterns in electroencephalography power spectrum and autism-related behaviors in a rat model of fragile X syndrome.

Fragile X syndrome (FXS), a neurodevelopmental disorder with autistic features, is caused by the loss of the fragile X mental retardation protein. Sex-specific differences in the clinical profile have been observed in FXS patients, but few studies have directly compared males and females in rodent models of FXS. To address this, we performed electroencephalography (EEG) recordings and a battery of autism-related behavioral tasks on juvenile and young adult Fmr1 knockout (KO) rats. EEG analysis demonstrated that compared to wild-type, male Fmr1 KO rats showed an increase in gamma frequency band power in the frontal cortex during the sleep-like immobile state, and both male and female KO rats failed to show an increase in delta frequency power in the sleep-like state, as observed in wild-type rats. Previous studies of EEG profiles in FXS subjects also reported abnormally increased gamma frequency band power, highlighting this parameter as a potential translatable biomarker. Both male and female Fmr1 KO rats displayed reduced exploratory behaviors in the center zone of the open field test, and increased distance travelled in an analysis of 24-h home cage activity, an effect that was more prominent during the nocturnal phase. Reduced wins against wild-type opponents in the tube test of social dominance was seen in both sexes. In contrast, increased repetitive behaviors in the wood chew test was observed in male but not female KO rats, while increased freezing in a fear conditioning test was observed only in the female KO rats. Our findings highlight sex differences between male and female Fmr1 KO rats, and indicate that the rat model of FXS could be a useful tool for the development of new therapeutics for treating this debilitating neurodevelopmental disorder.

Language prediction mechanisms in human auditory cortex.

Spoken language, both perception and production, is thought to be facilitated by an ensemble of predictive mechanisms. We obtain intracranial recordings in 37 patients using depth probes implanted along the anteroposterior extent of the supratemporal plane during rhythm listening, speech perception, and speech production. These reveal two predictive mechanisms in early auditory cortex with distinct anatomical and functional characteristics. The first, localized to bilateral Heschl's gyri and indexed by low-frequency phase, predicts the timing of acoustic events. The second, localized to planum temporale only in language-dominant cortex and indexed by high-gamma power, shows a transient response to acoustic stimuli that is uniquely suppressed during speech production. Chronometric stimulation of Heschl's gyrus selectively disrupts speech perception, while stimulation of planum temporale selectively disrupts speech production. This work illuminates the fundamental acoustic infrastructure-both architecture and function-for spoken language, grounding cognitive models of speech perception and production in human neurobiology.

Deficits in auditory predictive coding in individuals with the psychosis risk syndrome: Prediction of conversion to psychosis.

The mismatch negativity (MMN) event-related potential (ERP) component is increasingly viewed as a prediction error signal elicited when a deviant sound violates the prediction that a frequent "standard" sound will repeat. Support for this predictive coding framework emerged with the identification of the repetition positivity (RP), a standard stimulus ERP component that increases with standard repetition and is thought to reflect strengthening of the standard's memory trace and associated predictive code. Using electroencephalographic recordings, we examined the RP elicited by repeating standard tones presented during a traditional "constant standard" MMN paradigm in individuals with the psychosis risk syndrome (PRS; n = 579) and healthy controls (HC; n = 241). Clinical follow-up assessments identified PRS participants who converted to a psychotic disorder (n = 77) and PRS nonconverters who were followed for the entire 24-month clinical follow-up period and either remained symptomatic (n = 144) or remitted from the PRS (n = 94). In HC, RP linearly increased from early- to late-appearing standards within local trains of repeating standards (p < .0001), consistent with auditory predictive code/memory trace strengthening. Relative to HC, PRS participants showed a reduced RP across standards (p = .0056). PRS converters showed a relatively small RP deficit for early appearing standards relative to HC (p = .0.0107) and a more prominent deficit for late-appearing standards (p = .0006) relative to both HC and PRS-remitted groups. Moreover, greater RP deficits predicted shorter time to conversion in a subsample of unmedicated PRS individuals (p = .02). Thus, auditory predictive coding/memory trace deficits precede psychosis onset and predict future psychosis risk in PRS individuals. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Functional organization of mouse primary auditory cortex in adult C57BL/6 and F1 (CBAxC57) mice.

The primary auditory cortex (A1) plays a key role for sound perception since it represents one of the first cortical processing stations for sounds. Recent studies have shown that on the cellular level the frequency organization of A1 is more heterogeneous than previously appreciated. However, many of these studies were performed in mice on the C57BL/6 background which develop high frequency hearing loss with age making them a less optimal choice for auditory research. In contrast, mice on the CBA background retain better hearing sensitivity in old age. Since potential strain differences could exist in A1 organization between strains, we performed comparative analysis of neuronal populations in A1 of adult (~ 10 weeks) C57BL/6 mice and F1 (CBAxC57) mice. We used in vivo 2-photon imaging of pyramidal neurons in cortical layers L4 and L2/3 of awake mouse primary auditory cortex (A1) to characterize the populations of neurons that were active to tonal stimuli. Pure tones recruited neurons of widely ranging frequency preference in both layers and strains with neurons in F1 (CBAxC57) mice exhibiting a wider range of frequency preference particularly to higher frequencies. Frequency selectivity was slightly higher in C57BL/6 mice while neurons in F1 (CBAxC57) mice showed a greater sound-level sensitivity. The spatial heterogeneity of frequency preference was present in both strains with F1 (CBAxC57) mice exhibiting higher tuning diversity across all measured length scales. Our results demonstrate that the tone evoked responses and frequency representation in A1 of adult C57BL/6 and F1 (CBAxC57) mice are largely similar.

Reduced auditory steady state responses in autism spectrum disorder.

BACKGROUND: Auditory steady state responses (ASSRs) are elicited by clicktrains or amplitude-modulated tones, which entrain auditory cortex at their specific modulation rate. Previous research has reported reductions in ASSRs at 40 Hz for autism spectrum disorder (ASD) participants and first-degree relatives of people diagnosed with ASD (Mol Autism. 2011;2:11, Biol Psychiatry. 2007;62:192-197). METHODS: Using a 1.5 s-long auditory clicktrain stimulus, designed to elicit an ASSR at 40 Hz, this study attempted to replicate and extend these findings. Magnetencephalography (MEG) data were collected from 18 adolescent ASD participants and 18 typically developing controls. RESULTS: The ASSR localised to bilateral primary auditory regions. Regions of interest were thus defined in left and right primary auditory cortex (A1). While the transient gamma-band response (tGBR) from 0-0.1 s following presentation of the clicktrain stimulus was not different between groups, for either left or right A1, the ASD group had reduced oscillatory power at 40 Hz from 0.5 to 1.5 s post-stimulus onset, for both left and right A1. Additionally, the ASD group had reduced inter-trial coherence (phase consistency over trials) at 40 Hz from 0.64-0.82 s for right A1 and 1.04-1.22 s for left A1. LIMITATIONS: In this study, we did not conduct a clinical autism assessment (e.g. the ADOS), and therefore, it remains unclear whether ASSR power and/or ITC are associated with the clinical symptoms of ASD. CONCLUSION: Overall, our results support a specific reduction in ASSR oscillatory power and inter-trial coherence in ASD, rather than a generalised deficit in gamma-band responses. We argue that this could reflect a developmentally relevant reduction in non-linear neural processing.

Long-term effect of middle ear disease on temporal processing and P300 in two different populations of children.

BACKGROUND/OBJECTIVE: The effects of otitis media on the function of the central auditory nervous system in different populations is unknown. Understanding how the history of otitis media affects children from different nations will guide health professionals worldwide on the importance of adequate auditory stimulus in childhood. For this reason, the aim of the present study was to investigate the long-term auditory effects of middle ear disease on temporal processing and P300 in two different populations of children: Australian and Brazilian. METHODS: Temporal processing tests (Frequency Pattern Tests-FPT and Gaps in noise-GIN) and P300 were measured in 68 Brazilian and Australian children, aged between 8 to 14 years. The Brazilian otitis media group (BrOM) and Australian otitis media group (AusOM) consisted of 20 children each who had a documented history of otitis media. Control groups of 14 children (BrControl and AusControl) were also recruited from each country, all with no documented history of otitis media. RESULTS: The BrOM group showed significantly poorer performance (p<0.001) for FPT and the GIN compared to BrControl. The P300 response showed significantly longer mean latencies (p = 0.02) compared to BrControls. The AusOM group also showed significant delayed latency of P300 (p = 0.04) compared to the AusControl. The FPT showed significantly poorer performance (p = 0.04) compared to AusControls. The two otitis media groups showed no significant differences between each other on P300. Significant differences were seen however in temporal processing tests performance between the two cohorts for the otitis media groups. The BrOM group had significantly poorer responses (p<0.001) for FPT and GIN compared to the AusOM group. CONCLUSIONS: These findings support that although differences exist between BrOM and AusOM groups, otitis media can be demonstrated to affect the underlying mechanisms of the P300 measures and behavioral auditory responses in two different populations of children.

An unperceived acoustic stimulus decreases reaction time to visual information in a patient with cortical deafness.

Responding to multiple stimuli of different modalities has been shown to reduce reaction time (RT), yet many different processes can potentially contribute to multisensory response enhancement. To investigate the neural circuits involved in voluntary response initiation, an acoustic stimulus of varying intensities (80, 105, or 120 dB) was presented during a visual RT task to a patient with profound bilateral cortical deafness and an intact auditory brainstem response. Despite being unable to consciously perceive sound, RT was reliably shortened (~100 ms) on trials where the unperceived acoustic stimulus was presented, confirming the presence of multisensory response enhancement. Although the exact locus of this enhancement is unclear, these results cannot be attributed to involvement of the auditory cortex. Thus, these data provide new and compelling evidence that activation from subcortical auditory processing circuits can contribute to other cortical or subcortical areas responsible for the initiation of a response, without the need for conscious perception.

Cortical Tonotopic Map Changes in Humans Are Larger in Hearing Loss Than in Additional Tinnitus.

Neural plasticity due to hearing loss results in tonotopic map changes. Several studies have suggested a relation between hearing loss-induced tonotopic reorganization and tinnitus. This large fMRI study on humans was intended to clarify the relations between hearing loss, tinnitus, and tonotopic reorganization. To determine the differential effect of hearing loss and tinnitus, both male and female participants with bilateral high-frequency hearing loss, with and without tinnitus, and a control group were included. In a total of 90 participants, bilateral cortical responses to sound stimulation were measured with loudness-matched pure-tone stimuli (0.25-8 kHz). In the bilateral auditory cortices, the high-frequency sound-evoked activation level was higher in both hearing-impaired participant groups, compared with the control group. This was most prominent in the hearing loss group without tinnitus. Similarly, the tonotopic maps for the hearing loss without tinnitus group were significantly different from the controls, whereas the maps of those with tinnitus were not. These results show that higher response amplitudes and map reorganization are a characteristic of hearing loss, not of tinnitus. Both tonotopic maps and response amplitudes of tinnitus participants appear intermediate to the controls and hearing loss without tinnitus group. This observation suggests a connection between tinnitus and an incomplete form of central compensation to hearing loss, rather than excessive adaptation. One implication of this may be that treatments for tinnitus shift their focus toward enhancing the cortical plasticity, instead of reversing it.SIGNIFICANCE STATEMENT Tinnitus, a common and potentially devastating condition, is the presence of a "phantom" sound that often accompanies hearing loss. Hearing loss is known to induce plastic changes in cortical and subcortical areas. Although plasticity is a valuable trait that allows the human brain to rewire and recover from injury and sensory deprivation, it can lead to tinnitus as an unwanted side effect. In this large fMRI study, we provide evidence that tinnitus is related to a more conservative form of reorganization than in hearing loss without tinnitus. This result contrasts with the previous notion that tinnitus is related to excessive reorganization. As a consequence, treatments for tinnitus may need to enhance the cortical plasticity, rather than reverse it.

Multielectrode array analysis of EEG biomarkers in a mouse model of Fragile X Syndrome.

Fragile X Syndrome (FXS) is a leading known genetic cause of intellectual disability with symptoms that include increased anxiety and social and sensory processing deficits. Recent EEG studies in humans with FXS have identified neural oscillation deficits that include increased resting state gamma power, increased amplitude of auditory evoked potentials, and reduced inter-trial phase coherence of sound-evoked gamma oscillations. Identification of comparable EEG biomarkers in mouse models of FXS could facilitate the pre-clinical to clinical therapeutic pipeline. However, while human EEG studies have involved 128-channel scalp EEG acquisition, no mouse studies have been performed with more than three EEG channels. In the current study, we employed a recently developed 30-channel mouse multielectrode array (MEA) system to record and analyze resting and stimulus-evoked EEG signals in WT vs. Fmr1 KO mice. Using this system, we now report robust MEA-derived phenotypes including higher resting EEG power, altered event-related potentials (ERPs) and reduced inter-trial phase coherence to auditory chirp stimuli in Fmr1 KO mice that are remarkably similar to those reported in humans with FXS. We propose that the MEA system can be used for: (i) derivation of higher-level EEG parameters; (ii) EEG biomarkers for drug testing; and (ii) mechanistic studies of FXS pathophysiology.

A 7 Tesla fMRI investigation of human tinnitus percept in cortical and subcortical auditory areas.

Tinnitus is a clinical condition defined by hearing a sound in the absence of an objective source. Early experiments in animal models have suggested that tinnitus stems from an alteration of processing in the auditory system. However, translating these results to humans has proven challenging. One limiting factor has been the insufficient spatial resolution of non-invasive measurement techniques to investigate responses in subcortical auditory nuclei, like the inferior colliculus and the medial geniculate body (MGB). Here we employed ultra-high field functional magnetic resonance imaging (UHF-fMRI) at 7 Tesla to investigate the frequency-specific processing in sub-cortical and cortical regions in a cohort of six tinnitus patients and six hearing loss matched controls. We used task-based fMRI to perform tonotopic mapping and compared the magnitude and tuning of frequency-specific responses between the two groups. Additionally, we used resting-state fMRI to investigate the functional connectivity. Our results indicate frequency-unspecific reductions in the selectivity of frequency tuning that start at the level of the MGB and continue in the auditory cortex, as well as reduced thalamocortical and cortico-cortical connectivity with tinnitus. These findings suggest that tinnitus may be associated with reduced inhibition in the auditory pathway, potentially leading to increased neural noise and reduced functional connectivity. Moreover, these results indicate the relevance of high spatial resolution UHF-fMRI for the investigation of the role of sub-cortical auditory regions in tinnitus.

Deletion of Fmr1 from Forebrain Excitatory Neurons Triggers Abnormal Cellular, EEG, and Behavioral Phenotypes in the Auditory Cortex of a Mouse Model of Fragile X Syndrome.

Fragile X syndrome (FXS) is a leading genetic cause of autism with symptoms that include sensory processing deficits. In both humans with FXS and a mouse model [Fmr1 knockout (KO) mouse], electroencephalographic (EEG) recordings show enhanced resting state gamma power and reduced sound-evoked gamma synchrony. We previously showed that elevated levels of matrix metalloproteinase-9 (MMP-9) may contribute to these phenotypes by affecting perineuronal nets (PNNs) around parvalbumin (PV) interneurons in the auditory cortex of Fmr1 KO mice. However, how different cell types within local cortical circuits contribute to these deficits is not known. Here, we examined whether Fmr1 deletion in forebrain excitatory neurons affects neural oscillations, MMP-9 activity, and PV/PNN expression in the auditory cortex. We found that cortical MMP-9 gelatinase activity, mTOR/Akt phosphorylation, and resting EEG gamma power were enhanced in CreNex1/Fmr1Flox/y conditional KO (cKO) mice, whereas the density of PV/PNN cells was reduced. The CreNex1/Fmr1Flox/y cKO mice also show increased locomotor activity, but not the anxiety-like behaviors. These results indicate that fragile X mental retardation protein changes in excitatory neurons in the cortex are sufficient to elicit cellular, electrophysiological, and behavioral phenotypes in Fmr1 KO mice. More broadly, these results indicate that local cortical circuit abnormalities contribute to sensory processing deficits in autism spectrum disorders.

Impaired Subcortical Detection of Auditory Changes in Schizophrenia but Not in Major Depression.

The mismatch negativity is a cortical response to auditory changes and its reduction is a consistent finding in schizophrenia. Recent evidence revealed that the human brain detects auditory changes already at subcortical stages of the auditory pathway. This finding, however, raises the question where in the auditory hierarchy the schizophrenic deficit first evolves and whether the well-known cortical deficit may be a consequence of dysfunction at lower hierarchical levels. Finally, it should be resolved whether mismatch profiles differ between schizophrenia and affective disorders which exhibit auditory processing deficits as well. We used functional magnetic resonance imaging to assess auditory mismatch processing in 29 patients with schizophrenia, 27 patients with major depression, and 31 healthy control subjects. Analysis included whole-brain activation, region of interest, path and connectivity analysis. In schizophrenia, mismatch deficits emerged at all stages of the auditory pathway including the inferior colliculus, thalamus, auditory, and prefrontal cortex. In depression, deficits were observed in the prefrontal cortex only. Path analysis revealed that activation deficits propagated from subcortical to cortical nodes in a feed-forward mechanism. Finally, both patient groups exhibited reduced connectivity along this processing stream. Auditory mismatch impairments in schizophrenia already manifest at the subcortical level. Moreover, subcortical deficits contribute to the well-known cortical deficits and show specificity for schizophrenia. In contrast, depression is associated with cortical dysfunction only. Hence, schizophrenia and major depression exhibit different neural profiles of sensory processing deficits. Our findings add to a converging body of evidence for brainstem and thalamic dysfunction as a hallmark of schizophrenia.

Preserved Serotonergic Activity in Early-Onset Parkinson's Disease.

BACKGROUND: Serotonergic dysfunction may play an important role in motor and nonmotor symptoms of Parkinson's disease (PD). The loudness dependence of auditory evoked potentials (LDAEP) has been used to evaluate serotonergic activity. Therefore, this study aimed to determine central serotonergic activity using LDAEP in de novo PD according to the age at onset and changes in serotonergic activity after dopaminergic treatment. METHODS: A total of 30 patients with unmedicated PD, 16 in the early-onset and 14 in the late-onset groups, were enrolled. All subjects underwent comprehensive neurological examination, laboratory tests, the Unified Parkinson's Disease Rating Scale, and LDAEP. The LDAEP was calculated as the slope of the two N1/P2 peaks measured at the Cz electrode, first at baseline conditions (pretreatment) and a second time after 12 weeks (post-treatment) following dopaminergic medications. RESULTS: The absolute values of pretreatment N1/P2 LDAEP (early-onset: late-onset, 0.99 ± 0.68: 1.62 ± 0.88, p = 0.035) and post-treatment N1 LDAEP (early-onset: late-onset, -0.61 ± 0.61: -1.26 ± 0.91, p = 0.03) were significantly lower in the early-onset group compared with those of the late-onset group. In addition, a higher value of pretreatment N1/P2 LDAEP was significantly correlated with the late-onset group (coefficient = 1.204, p = 0.044). The absolute value of the N1 LDAEP decreased after 12 weeks of taking dopaminergic medication (pretreatment: post-treatment, -1.457 ± 1.078: -0.904 ± 0.812, p = 0.0018). CONCLUSIONS: Based on the results of this study, LDAEP could be a marker for serotonergic neurotransmission in PD. Central serotonergic activity assessed by LDAEP may be more preserved in early-onset PD patients and can be altered with dopaminergic medication.

Reorganization of Sound Location Processing in the Auditory Cortex of Blind Humans.

Auditory spatial tasks induce functional activation in the occipital-visual-cortex of early blind humans. Less is known about the effects of blindness on auditory spatial processing in the temporal-auditory-cortex. Here, we investigated spatial (azimuth) processing in congenitally and early blind humans with a phase-encoding functional magnetic resonance imaging (fMRI) paradigm. Our results show that functional activation in response to sounds in general-independent of sound location-was stronger in the occipital cortex but reduced in the medial temporal cortex of blind participants in comparison with sighted participants. Additionally, activation patterns for binaural spatial processing were different for sighted and blind participants in planum temporale. Finally, fMRI responses in the auditory cortex of blind individuals carried less information on sound azimuth position than those in sighted individuals, as assessed with a 2-channel, opponent coding model for the cortical representation of sound azimuth. These results indicate that early visual deprivation results in reorganization of binaural spatial processing in the auditory cortex and that blind individuals may rely on alternative mechanisms for processing azimuth position.