Auditory Gating Research Articles

Auditory gating and its clinical correlates in adults with chronic tic disorder and neurotypical adults

BackgroundOver 80% of adults with chronic tic disorder (CTD) experience sensory over-responsivity (SOR), defined as heightened awareness of and/or behavioral reactivity to commonplace environmental stimuli. One potential mechanism underpinning SOR is sensory gating impairment. Sensory gating is the physiologic process whereby redundant stimuli are filtered out in early perceptual stages. In this study, we compared sensory gating between neurotypical and CTD adults and determined if gating indices associated with SOR. MethodsNeurotypical (n = 31) and CTD adults (n = 26) completed a clinical assessment, including two SOR measures (Sensory Gating Inventory, SGI; Sensory Perception Quotient, SPQ), and an auditory gating paradigm while monitored on EEG. ResultsCTD adults exhibited greater SOR. Neurotypical and CTD adults did not differ in P50, N100, or P200 gating ratios. In regression analyses, N100 gating ratio was significantly associated with SGI score; the magnitude of this association was greater for neurotypical than CTD adults. No other significant associations emerged between gating ratios and SOR measures. ConclusionFindings do not support sensory gating impairment as a mechanism underpinning SOR in CTD.The relationship between N100 gating and SOR warrants further investigation. SignificanceThis is the first study to examine auditory gating in individuals with CTD.

Auditory Sensory Gating: Effects of Noise.

Cortical auditory evoked potentials (CAEPs) indicate that noise degrades auditory neural encoding, causing decreased peak amplitude and increased peak latency. Different types of noise affect CAEP responses, with greater informational masking causing additional degradation. In noisy conditions, attention can improve target signals' neural encoding, reflected by an increased CAEP amplitude, which may be facilitated through various inhibitory mechanisms at both pre-attentive and attentive levels. While previous research has mainly focused on inhibition effects during attentive auditory processing in noise, the impact of noise on the neural response during the pre-attentive phase remains unclear. Therefore, this preliminary study aimed to assess the auditory gating response, reflective of the sensory inhibitory stage, to repeated vowel pairs presented in background noise. CAEPs were recorded via high-density EEG in fifteen normal-hearing adults in quiet and noise conditions with low and high informational masking. The difference between the average CAEP peak amplitude evoked by each vowel in the pair was compared across conditions. Scalp maps were generated to observe general cortical inhibitory networks in each condition. Significant gating occurred in quiet, while noise conditions resulted in a significantly decreased gating response. The gating function was significantly degraded in noise with less informational masking content, coinciding with a reduced activation of inhibitory gating networks. These findings illustrate the adverse effect of noise on pre-attentive inhibition related to speech perception.

Influence of GABAA and GABAB receptor activation on auditory sensory gating and its association with anxiety in healthy volunteers.

Dysfunctional sensory gating in anxiety disorders, indexed by the failure to inhibit the P50 event-related potential (ERP) to repeated stimuli, has been linked to deficits in the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). This study, conducted in 30 healthy volunteers, examined the acute effects of GABAA (lorazepam: 1 mg) and GABAB receptor (baclofen: 10 mg) agonists on P50 measures of auditory sensory gating within a paired-stimulus (S1-S2) paradigm and assessed changes in gating in relation to self-ratings of anxiety. Compared to placebo, lorazepam reduced ERP indices of sensory gating by attenuating response to S1. Although not directly impacting P50 inhibition, baclofen-induced changes in gating (relative to placebo) were negatively correlated with trait but not state anxiety. These preliminary findings support the involvement of GABA in sensory gating and tentatively suggest a role for GABAB receptor signaling in anxiety-associated gating dysregulation.

Auditory P50 Sensory Gating Alterations in Major Depressive Disorder and their Relationship to Clinical Symptoms

Cognitive deficits in depression are pervasive and include impairments in attention and higher-order functions but the degree to which low-level sensory processes are affected is unclear. The present work examined event-related potential (P50 and N100) features of auditory sensory gating (i.e., the ability to inhibit P50/N100 responses to redundant stimuli) and their relationship to depressive symptoms, including ruminations and dysfunctional attitudes. In 18 patients with major depressive disorder (MDD) and 18 healthy volunteers, auditory sensory gating was measured using a paired-stimulus paradigm yielding ratio (rP50, rN100) and difference (dP50, dN100) gating indices, which reflected amplitude reductions from first (S1) to second (S2) stimulus. Patients with MDD exhibited diminished rP50 and dP50 gating scores and delayed S1-N100 latencies compared to healthy volunteers. These measures were positively associated with ruminative thoughts, negative attitudes and degree of depression. Study findings implicate aberrant sensory processing in depressed patients that is related to severity of maladaptive thinking.

Unraveling the contributions of prosodic patterns and individual traits on cross-linguistic perception of Spanish sentence modality.

Cross-linguistic perception is known to be molded by native and second language (L2) experiences. Yet, the role of prosodic patterns and individual characteristics on how speakers of tonal languages perceive L2 Spanish sentence modalities remains relatively underexplored. This study addresses the gap by analyzing the auditory performance of 75 Mandarin speakers with varying levels of Spanish proficiency. The experiment consisted of four parts: the first three collected sociolinguistic profiles and assessed participants' pragmatic competence and musical abilities. The last part involved an auditory gating task, where participants were asked to identify Spanish broad focus statements and information-seeking yes/no questions with different stress patterns. Results indicated that the shape of intonation contours and the position of the final stressed syllable significantly impact learners' perceptual accuracy, with effects modulated by utterance length and L2 proficiency. Moreover, individual differences in pragmatic and musical competence were found to refine auditory and cognitive processing in Mandarin learners, thereby influencing their ability to discriminate question-statement contrasts. These findings reveal the complex interplay between prosodic and individual variations in L2 speech perception, providing novel insights into how speakers of tonal languages process intonation in a non-native Romance language like Spanish.

Allosteric Activation of α7 Nicotinic Acetylcholine Receptors by Novel 2-Arylamino-thiazole-5-carboxylic Acid Amide Derivatives for the Improvement of Cognitive Deficits in Mice.

Enhancing α7 nAChR function serves as a therapeutic strategy for cognitive disorders. Here, we report the synthesis and evaluation of 2-arylamino-thiazole-5-carboxylic acid amide derivatives 6-9 that as positive allosteric modulators (PAMs) activate human α7 nAChR current expressed in Xenopus ooctyes. Among the 4-amino derivatives, a representative atypical type I PAM 6p exhibits potent activation of α7 current with an EC50 of 1.3 μM and the maximum activation effect on the current over 48-fold in the presence of acetylcholine (100 μM). The structure-activity relationship (SAR) analysis reveals that the 4-amino group is crucial for the allosteric activation of α7 currents by compound 6p as the substitution of 4-methyl group results in its conversion to compound 7b (EC50 = 2.1 μM; max effect: 58-fold) characterized as a typical type I PAM. Furthermore, both 6p and 7b are able to rescue auditory gating deficits in mouse schizophrenia-like model of acoustic startle prepulse inhibition.

Sensory Gating Networks in Normal-Hearing Adults With Minimal Tinnitus.

The goal of this study was to observe sensory gating-related networks underlying cortical auditory evoked potential (CAEP) peak components in individuals with and without minimal tinnitus, as measured using the Tinnitus Handicap Inventory (THI). This analysis was performed on previously published sensory gating responses in normal-hearing adults with and without minimal tinnitus. Independent component analysis was performed for each individual CAEP gating component (Pa, P50, N1, and P2). Significant components were retained for source localization analyses within the following groups: no tinnitus, tinnitus with a THI score ≤ 6, and tinnitus with a THI score > 6. Brain source localization was performed on the gating difference wave for each component using standardized low-resolution brain electromagnetic tomography. Gating-related networks were identified within each group. Different regional sources were observed between groups, with parietal sources underlying the Pa and P50 components as tinnitus severity increased. A larger prefrontal regional activation was also shown for the N1 gating component as tinnitus severity increased. These results expand upon the functional gating responses via CAEP waveforms in a previously published study. The auditory gating response, as measured via CAEPs, has previously been shown to significantly correlate with an increase in tinnitus severity in adults with normal hearing. The corresponding changes in the gating response appear to be supported by different cortical regions in those without tinnitus, those with a THI score ≤ 6, and those with a THI score > 6. Next, functional differences between localized cortical regions should be tested.

Unraveling the role of Slc10a4 in auditory processing and sensory motor gating: Implications for neuropsychiatric disorders?

BackgroundPsychiatric disorders, such as schizophrenia, are complex and challenging to study, partly due to the lack of suitable animal models. However, the absence of the Slc10a4 gene, which codes for a monoaminergic and cholinergic associated vesicular transporter protein, in knockout mice (Slc10a4−/−), leads to the accumulation of extracellular dopamine. A major challenge for studying schizophrenia is the lack of suitable animal models that accurately represent the disorder. We sought to overcome this challenge by using Slc10a4−/− mice as a potential model, considering their altered dopamine levels. This makes them a potential animal model for schizophrenia, a disorder known to be associated with altered dopamine signaling in the brain. MethodsThe locomotion, auditory sensory filtering and prepulse inhibition (PPI) of Slc10a4−/− mice were quantified and compared to wildtype (WT) littermates. Intrahippocampal electrodes were used to record auditory event-related potentials (aERPs) for quantifying sensory filtering in response to paired-clicks. The channel above aERPs phase reversal was chosen for reliably comparing results between animals, and aERPs amplitude and latency of click responses were quantified. WT and Slc10a4−/− mice were also administered subanesthetic doses of ketamine to provoke psychomimetic behavior. ResultsBaseline locomotion during auditory stimulation was similar between Slc10a4−/− mice and WT littermates. In WT animals, normal auditory processing was observed after i.p saline injections, and it was maintained under the influence of 5 mg/kg ketamine, but disrupted by 20 mg/kg ketamine. On the other hand, Slc10a4−/− mice did not show significant differences between N40 S1 and S2 amplitude responses in saline or low dose ketamine treatment. Auditory gating was considered preserved since the second N40 peak was consistently suppressed, but with increased latency. The P80 component showed higher amplitude, with shorter S2 latency under saline and 5 mg/kg ketamine treatment in Slc10a4−/− mice, which was not observed in WT littermates. Prepulse inhibition was also decreased in Slc10a4−/− mice when the longer interstimulus interval of 100 ms was applied, compared to WT littermates. ConclusionThe Slc10a4−/− mice responses indicate that cholinergic and monoaminergic systems participate in the PPI magnitude, in the temporal coding (response latency) of the auditory sensory gating component N40, and in the amplitude of aERPs P80 component. These results suggest that Slc10a4−/− mice can be considered as potential models for neuropsychiatric conditions.

Alterations of auditory sensory gating in mice with noise-induced tinnitus treated with nicotine and cannabis extract.

Tinnitus is a phantom sound perception affecting both auditory and limbic structures. The mechanisms of tinnitus remain unclear and it is debatable whether tinnitus alters attention to sound and the ability to inhibit repetitive sounds, a phenomenon also known as auditory gating. Here we investigate if noise exposure interferes with auditory gating and whether natural extracts of cannabis or nicotine could improve auditory pre-attentional processing in noise-exposed mice. We used 22 male C57BL/6J mice divided into noise-exposed (exposed to a 9-11 kHz narrow band noise for 1 h) and sham (no sound during noise exposure) groups. Hearing thresholds were measured using auditory brainstem responses, and tinnitus-like behavior was assessed using Gap prepulse inhibition of acoustic startle. After noise exposure, mice were implanted with multi-electrodes in the dorsal hippocampus to assess auditory event-related potentials in response to paired clicks. The results showed that mice with tinnitus-like behavior displayed auditory gating of repetitive clicks, but with larger amplitudes and longer latencies of the N40 component of the aERP waveform. The combination of cannabis extract and nicotine improved the auditory gating ratio in noise-exposed mice without permanent hearing threshold shifts. Lastly, the longer latency of the N40 component appears due to an increased sensitivity to cannabis extract in noise-exposed mice compared to sham mice. The study suggests that the altered central plasticity in tinnitus is more sensitive to the combined actions on the cholinergic and the endocannabinoid systems. Overall, the findings contribute to a better understanding of pharmacological modulation of auditory sensory gating.

Atypical function of auditory sensory gating in children with developmental dyslexia: Investigating its relationship with cognitive abilities.

Impairments of auditory processing are among frequent findings in dyslexia. However, it is unclear how auditory signals are gated from brainstem to higher central processing stages in these individuals. The present study was done to investigate auditory sensory gating in children with developmental dyslexia (DD), and to determine whether sensory gating correlates with performance on behavioural tasks. Auditory sensory gating at P50, N1 and P2 waves was evaluated in two groups including 20 children with DD and 19 children with typical reading development (TRD). Behavioural tests were used to evaluate phonological working memory (PWM) and selective attention abilities. Sensory gating in children with DD was significantly less efficient than their peers at P50, N1 and P2 waves. Lower auditory evoked potential (AEP) amplitudes were found in the DD group. The children with TRD scored better in all the behavioural tests. Relationships were reported between sensory gating at P50, N1, P2 and behavioural performance in the two groups. Children with dyslexia had deficient sensory gating in comparison with controls. In addition, children with dyslexia experienced problems with PWM and selective attention tasks. The function of sensory gating was associated with attentional and PWM performances in this group.

469 Electroencephalographic Correlate of Sensory Over-Responsivity in Adults with Chronic Tic Disorders

OBJECTIVES/GOALS: To identify an electroencephalographic (EEG) signature of SOR in adults with TS METHODS/STUDY POPULATION: We will recruit 60 adults with CTD and 60 sex- and age-matched healthy controls to complete scales assessing severity of SOR (Sensory Gating Inventory, SGI), tics, and psychiatric symptoms. Subjects will then be monitored on dense-array scalp EEG during sequential auditory and tactile sensory gating paradigms, as such paradigms have been shown to correlate with self-report measures of SOR in other populations. Single-trial EEG data will be segmented into 100-ms epochs and spectrally deconvoluted into standard frequency bands (delta, theta, alpha, beta, gamma) for pre-defined regions of interest. We will conduct between-group contrasts (Wilcoxon rank-sum) of band-specific sensory gating indices and within-group correlations (Spearman rank correlations) between sensory gating indices and SGI scores. RESULTS/ANTICIPATED RESULTS: We hypothesize that, relative to controls, adults with CTD exhibit impaired sensory gating and that extent of impairment correlates with severity of SOR. 14 adults with CTD (9 men, 5 women) and 16 controls (10 men, 6 women) have completed the protocol to date. Within this sample, adults with CTD showed significantly reduced sensory gating compared to controls in frontal (CTD median 0.12 dB (interquartile range -0.15–0.70 dB); control -0.37 dB (-0.80–-0.13 dB); p = 0.01) and parietal (CTD 0.17 dB (-0.08–0.50 dB); control -0.20 dB (-0.43–0.10 dB); p = 0.01) gamma band during the 100-200 ms epoch in the tactile paradigm. No significant between-group differences were evident for the auditory paradigm. Among adults with CTD, multiple sensory gating indices significantly correlated with SGI scores. Enrollment continues. DISCUSSION/SIGNIFICANCE: Results aim to clarify the extent of sensory gating impairment in TS and identify a clinical correlate of neurophysiologic dysfunction in the disorder. Such knowledge has direct implications for identification of candidate neurophysiologic biomarkers, an express goal of the National Institutes of Health.

Cortical and thalamic modulation of auditory gating in the posterior parietal cortex of awake mice.

Auditory gating (AG) is an adaptive mechanism for filtering out redundant acoustic stimuli to protect the brain against information overload. AG deficits have been found in many mental illnesses, including schizophrenia (SZ). However, the neural correlates of AG remain poorly understood. Here, we found that the posterior parietal cortex (PPC) shows an intermediate level of AG in auditory thalamocortical circuits, with a laminar profile in which the strongest AG is in the granular layer. Furthermore, AG of the PPC was decreased and increased by optogenetic inactivation of the medial dorsal thalamic nucleus (MD) and auditory cortex (AC), respectively. Optogenetically activating the axons from the MD and AC drove neural activities in the PPC without an obvious AG. These results indicated that AG in the PPC is determined by the integrated signal streams from the MD and AC in a bottom-up manner. We also found that a mouse model of SZ (postnatal administration of noncompetitive N-methyl-d-aspartate receptor antagonist) presented an AG deficit in the PPC, which may be inherited from the dysfunction of MD. Together, our findings reveal a neural circuit underlying the generation of AG in the PPC and its involvement in the AG deficit of SZ.

Song-related brain auditory activity in Bengalese finches as examined by immediate early gene expressions: Comparison of arousal states and the correlational analyses between brain regions

Songbirds use auditory feedback to memorize a tutor song in juveniles and to maintain it in adults. In Bengalese finches, electrophysiological studies showed the auditory responses in the premotor area HVC remained active regardless of asleep/awake status, in contrast to auditory gating phenomenon identified in zebra finches. We investigated the correlations in auditory activity between the brain regions and differences in the activity during wakefulness and sleeping in Bengalese finches. We used the immediate early gene egr-1 as a marker of neural activity that can detect regions responding to auditory stimuli in the whole brain. Results showed that auditory response, as measured by egr-1 expression to the bird’s own song while sleeping and awake, was similar in HVC and NCM. Higher activity during awake than sleep was found only in the lower auditory area MLd. Analyses showed egr-1 expressions between brain regions induced by the bird’s own song playback in awake/sleep conditions, suggesting that auditory information correlated with the inter part, not the outer part, of MLd with the higher song-related regions. Furthermore, the sleep condition suppressed the spontaneous activity, but not the song-induced activity in Area X. Altogether, this study presents a new attempt to explore the auditory-motor network using a molecular tool to map neurons of the nearly whole brain.

Neural Mechanisms of the Acceptable Noise Level.

The present brain-behavior study examined whether sensory registration or neural inhibition processes explained variability in the behavioral most comfortable level (MCL) and background noise level (BNL) components of the acceptable noise level (ANL) measure. A traditional auditory gating paradigm was used to evoke neural responses to pairs of pure-tone stimuli in 32 adult listeners with normal hearing. Relationships between behavioral ANL, MCL, and BNL components and cortical responses to each of the paired stimuli were analyzed using linear mixed-effects regression analyses. Neural responses elicited by Stimulus 2 in the gating paradigm significantly predicted the computed ANL response. The MCL component was significantly associated with responses elicited by Stimulus 1 of the pair. The BNL component of the ANL was significantly associated with neural responses to both Stimulus 1 and Stimulus 2. The results suggest neural processes related to neural inhibition support the ANL and BNL component while neural stimulus registration properties are associated with the MCL a listener chooses. These findings suggest that differential neural mechanisms underlie the separate MCL and BNL components of the ANL response.

Principal component analysis of auditory ERPs discriminates mild cognitive impairment and Alzheimer’s disease from normal aging

AbstractBackgroundSensory gating refers to an inhibitory mechanism of the brain that protects higher cortical centers from being flooded with repetitive, redundant sensory inputs. Sensory gating is modulated by cholinergic transmission, the deterioration of which is a prominent neurochemical feature of Alzheimer’s disease (AD), the most common form of dementia in the elderly. The study investigated whether alterations in inhibitory gating, assessed by event‐related potentials (ERPs) in response to repeated auditory stimuli, can discriminate AD and mild cognitive impairment (MCI) from normal aging.MethodEvent‐related electroencephalogram was recorded from 38 AD patients, 37 MCI patients, and 38 elderly cognitively normal control (NC) participants in a conditioning–testing paradigm. ERP waveforms, stimulus‐locked changes in power, and inter‐trial phase clustering (ITPC) were extracted and submitted to a covariance‐based principal component analysis (PCA) to yield data‐driven component measures.ResultNon‐parametric cluster‐based permutation tests revealed statistically significant differences for ERP waveforms in separating AD, for power in separating AD and MCI, and for ITPC in separating AD, MCI, and NC from the other two groups pooled together.ConclusionThe study confirms that alterations in auditory sensory gating can discriminate between AD, MCI, and normal aging. Auditory ERPs might serve as an objective, non‐invasive, and cost‐effective method for evaluating cognitive decline suggestive of AD and to monitor disease progression, therapeutic efficacy, or effects of novel drug candidates in clinical trials.

Associations of the serum kynurenine pathway metabolites with P50 auditory gating in non-smoking patients with first-episode schizophrenia.

Our study aimed to investigate the associations between the serum level of kynurenine pathway (KP) metabolites and P50 auditory gating in non-smoking patients with first-episode schizophrenia (FES). In this study, 82 non-smoking patients with FES and 73 healthy controls (HC). P50 auditory gating was measured using a fully functional digital 64-channel EEG system, and the components included S1 amplitude, S2 amplitude, gating ratio (S2/S1), and amplitude difference (S1-S2). Serum levels of kynurenine and kynurenine acid were assessed using a combination of liquid chromatography with tandem mass spectrometry. Psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). The serum kynurenine (251.46 ± 65.93 ng/ml vs. 320.65 ± 65.89 ng/ml, t = -6.38, p < 0.001), and kynurenine acid levels (5.19 ± 2.22 ng/ml vs. 13.26 ± 4.23 ng/ml, t = -14.73, p < 0.001), S1 amplitude [2.88 (1.79, 3.78) μV vs. 3.08 (2.46, 4.56) μV, Z = -2.17, p = 0.030] and S1-S2 [1.60 (0.63, 2.49) μV vs. 1.92 (1.12, 2.93) μV, Z = -2.23, p = 0.026] in patients with FES were significantly lower than those in HC. The serum kynurenine and kynurenine acid levels were negatively associated with S1-S2 (r = -0.32, p = 0.004 and r = -0.42, p < 0.001; respectively) and positively correlated with S2/S1 ratio (r = 0.34, p = 0.002 and r = 0.35, p = 0.002; respectively) in patients. Our findings suggested that neuroactive metabolites of the KP might play an important role in sensory gating deficit in first episode patients with schizophrenia. Furthermore, metabolites of the KP may be a new target for the treatment of cognitive impairments in schizophrenia.

Largely unaffected auditory and visual sensory processing phenotypes in the evoked potentials of Fmr1 KO2 mice.

Sensory sensitivity symptoms are common in autism spectrum disorders and fragile X syndrome. Mainly in the auditory modality, disturbed processing has been found in both fragile X patients and the corresponding genetic mouse model, the Fmr1 knockout mouse. Here, we tried to replicate the auditory deficits and assess whether also visual processing is affected, using electroencephalography readouts under freely behaving conditions in the second-generation Fmr1 knockout mice. No differences between wild-type and knockout animals were found in single auditory and visual evoked potentials in response to pure sine tones and full-field light flashes. Visual sensory gating was enhanced in the early but not the late components of the evoked potentials, but no changes were found in auditory sensory gating. The higher harmonics of the synchronisation response to flickering visual stimuli seemed to be reduced with 10, but not 20 or 40 Hz, stimulation. However, this effect was not reproduced in an independent second cohort of animals. No synchronisation differences were found in response to a chirp stimulus, of which the frequency steadily increased. Taken together, this study could not reproduce earlier reported increased amplitudes in auditory responses, nor could it convincingly show that synchronisation deficits found to be present in the auditory modality also existed in the visual modality. The discrepancies within this study as well as between various studies assessing sensory processing in the Fmr1 KO raise questions about the external validity of these phenotypes and warrant careful interpretation of these phenotypes.

The Role of the Root in Spoken Word Recognition in Hebrew: An Auditory Gating Paradigm.

Very few studies have investigated online spoken word recognition in templatic languages. In this study, we investigated both lexical (neighborhood density and frequency) and morphological (role of root morpheme) aspects of spoken word recognition of Hebrew, a templatic language, using the traditional gating paradigm. Additionally, we compared the traditional gating paradigm with a novel, phoneme-based gating paradigm. The phoneme-based approach allows for better control of information available at each gate. We found lexical effects with high-frequency words and low neighborhood density words being recognized at earlier gates. We also found that earlier access to root-morpheme information enabled word recognition at earlier gates. Finally, we showed that both the traditional gating paradigm and gating by phoneme paradigm yielded equivalent results.

Risperidone on apomorphine-induced stereotyped behavior and auditory sensory gating in rhesus monkeys

The ameliorating effect of risperidone on apomorphine-induced stereotyped behavior and inhibition of auditory sensory gating was investigated using rhesus monkeys. The total duration of the stereotyped behavior observed in the control group was 43.7 ± 23.0 s (n = 3) between 10 and 25 min after vehicle administration, whereas the duration in the apomorphine-treated (0.1 or 0.15 mg/kg i.m., n = 3) group was observed to be significantly prolonged to 413.0 ± 150.6 s. Administration of 0.01, 0.03, 0.1 mg/kg of risperidone 60 min before apomorphine, significantly reduced the duration of this apomorphine-induced stereotyped behavior to 327 ± 104.9 s (n = 3), 8.3 ± 4.2 s (n = 3), and 0.0 ± × 0.0 s (n = 3, t-test: p < 0.05), respectively. Next, the auditory sensory gating test/conditioning (T/C) ratio was used as a bio-marker. The T/C ratio was 0.598 ± 0.0802 in the vehicle-administered control group (n = 4) and was significantly increased to 2.098 ± 0.254 (n = 4) by apomorphine (0.15 mg/kg, i.m.). Administering of risperidone (0.1 mg/kg, s.c.) 30 min before apomorphine treatment significantly restricted the T/C ratio to 0.571 ± 0.0886 (n = 4), compared to the T/C ratio in the vehicle-administered control group. The above results demonstrate, not only behaviorally but also electrophysiologically, the ameliorating effect of risperidone on the induction of schizophrenia-like symptoms by apomorphine in non-human primates.

N-methyl-D-aspartate receptor antagonism impairs sensory gating in the auditory cortex in response to speech stimuli.

Deficits in early auditory sensory processing in schizophrenia have been linked to N-methyl-D-aspartate receptor (NMDAR) hypofunction, but the role of NMDARs in aberrant auditory sensory gating (SG) in this disorder is unclear. This study, conducted in 22 healthy humans, examined the acute effects of a subanesthetic dose of the NMDAR antagonist ketamine on SG as measured electrophysiologically by suppression of the P50 event-related potential (ERP) to the second (S2) relative to the first (S1) of two closely paired (500ms) identical speech stimuli. Ketamine induced impairment in SG indices at sensor (scalp)-level and at source-level in the auditory cortex (as assessed with eLORETA). Together with preliminary evidence of modest positive associations between impaired gating and dissociative symptoms elicited by ketamine, tentatively support a model of NMDAR hypofunction underlying disturbances in auditory SG in schizophrenia.