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Modulating cortical excitability based on a stimulus’ relevance to the task at hand is a component of sensory gating, and serves to protect higher cortical centers from being overwhelmed with irrelevant information (McIlroy et al., 2003; Kumar et al., 2005; Wasaka et al., 2005). This study examined relevancy-based modulation of cortical excitability, and corresponding behavioral responses, in the face of distracting stimuli in participants with and without a history of concussion (mean age 22 ± 3 SD years; most recent concussion 39.1 ± 30 SD months). Participants were required to make a scaled motor response to the amplitudes of visual and tactile stimuli presented individually or concurrently. Task relevance was manipulated, and stimuli were occasionally presented with irrelevant distractors. Electroencephalography (EEG) and task accuracy data were collected from participants with and without a history of concussion. The somatosensory-evoked N70 event-related potential (ERP) was significantly modulated by task relevance in the control group but not in those with a history of concussion, and there was a significantly greater cost to task accuracy in the concussion history group when relevant stimuli were presented with an irrelevant distractor. This study demonstrated that relevancy-based modulation of electrophysiological responses and behavioral correlates of sensory gating differ in people with and without a history of concussion, even after patients were symptom-free and considered recovered from their injuries.

Sensory and sensorimotor gating deficits characterize both Tourette syndrome (TS) and schizophrenia. Premonitory urges (PU) in TS can be assessed with the University of Sao Paulo Sensory Phenomena Scale (USP-SPS) and the Premonitory Urge for Tics Scale (PUTS). In 40 subjects (TS: n = 18; healthy comparison subjects [HCS]: n = 22), we examined the relationship between PU scores and measures of sensory gating using the USP-SPS, PUTS, Sensory Gating Inventory (SGI), and Structured Interview for Assessing Perceptual Anomalies (SIAPA), as well symptom severity scales. SGI, but not SIAPA, scores were elevated in TS subjects (p < 0.0003). In TS subjects, USP-SPS and PUTS scores correlated significantly with each other, but not with the SGI or SIAPA; neither PU nor sensory gating scales correlated significantly with symptom severity. TS subjects endorse difficulties in sensory gating and the SGI may be valuable for studying these clinical phenomena.

Sensory gating (SG) is a well-studied phenomenon in which neural responses are reduced to identical stimuli presented in succession, and is thought to represent the functional inhibition of primary sensory information that is redundant in nature. SG is traditionally considered pre-attentive, but little is known about the effects of attentional state on this process. In this study, we investigate the impact of directed attention on somatosensory SG using magnetoencephalography. Healthy young adults (n ​= ​26) performed a novel somato-visual paired-pulse oddball paradigm, in which attention was directed towards or away from paired-pulse stimulation of the left median nerve. We observed a robust evoked (i.e., phase-locked) somatosensory response in the time domain, and three stereotyped oscillatory responses in the time-frequency domain including an early theta response (4–8 ​Hz), and later alpha (8–14 ​Hz) and beta (20–26 ​Hz) responses across attentional states. The amplitudes of the evoked response and the theta and beta oscillations were gated for the second stimulus, however, only the gating of the oscillatory responses was altered by attention. Specifically, directing attention to the somatosensory domain enhanced SG of the early theta response, while reducing SG of the later alpha and beta responses. Further, prefrontal alpha-band coherence with the primary somatosensory cortex was greater when attention was directed towards the somatosensory domain, supporting a frontal modulatory effect on the alpha response in primary somatosensory regions. These findings highlight the dynamic effects of attentional modulation on somatosensory processing, and the importance of considering attentional state in studies of SG.

Prepulse inhibition (PPI) may useful for exploring the proposed shared neurobiology between idiopathic autism and autism caused by FXS. We compared PPI in four groups: typically developing controls (n = 18), FXS and autism (FXS+A; n = 15), FXS without autism spectrum disorder (FXS-A; n = 17), and idiopathic autism (IA; n = 15). Relative to controls, the FXS+A (p < 0.002) and FXS-A (p < 0.003) groups had impaired PPI. The FXS+A (p < 0.01) and FXS-A (p < 0.03) groups had lower PPI than the IA group. Prolonged startle latency was seen in the IA group. The differing PPI profiles seen in the FXS+A and IA indicates these groups may not share a common neurobiological abnormality of sensorimotor gating.

Sensory and sensorimotor gating deficits characterize both Tourette syndrome (TS) and schizophrenia. Premonitory urges (PU) in TS can be assessed with the University of Sao Paulo Sensory Phenomena Scale (USP-SPS) and the Premonitory Urge for Tics Scale (PUTS). In 40 subjects (TS: n = 18; healthy comparison subjects [HCS]: n = 22), we examined the relationship between PU scores and measures of sensory gating using the USP-SPS, PUTS, Sensory Gating Inventory (SGI), and Structured Interview for Assessing Perceptual Anomalies (SIAPA), as well symptom severity scales. SGI, but not SIAPA, scores were elevated in TS subjects (p < 0.0003). In TS subjects, USP-SPS and PUTS scores correlated significantly with each other, but not with the SGI or SIAPA; neither PU nor sensory gating scales correlated significantly with symptom severity. TS subjects endorse difficulties in sensory gating and the SGI may be valuable for studying these clinical phenomena.

Measures of the brain’s automatic electrophysiological responses to sounds represent a potential tool for identifying age- and depression-related neural markers. However, these markers have rarely been studied related to aging and depression within one study. Here, we investigated auditory event-related potentials (ERPs) in the brain that may show different alterations related to aging and depression. We used an oddball condition employing changes in sound intensity to investigate: (i) sound intensity dependence; (ii) sensory gating; and (iii) change detection, all within a single paradigm. The ERPs of younger (18–40 years) and older (62–80 years) depressed female participants and age-matched non-depressed participants were measured. Intensity dependence was examined as the difference between N1 responses to repeated high- and low-intensity sounds, sensory gating as N1 responses to rare and repeated sounds, and change detection as indexed by the mismatch negativity (MMN). We found that intensity dependence was greater in older participants than younger ones, indicating effects related to aging but not to depression. For sensory gating, we found depression- and age-related alterations as increased N1 responses. No group differences were found for MMN. Although a sensory gating deficit was expected in older adults, this study is the first to demonstrate age-related overexcitability in sound intensity dependency. The results indicate that automatic brain responses to sound intensity changes are suitable for studying age- and depression-related neural markers but may not be sensitive enough to differentiate the effects of aging and depression.

Patients with amnestic mild cognitive impairment (aMCI) demonstrate significant cognitive deficits, especially in the memory aspect. The memory deficiency might be attributed to the difficulties in the inhibitory function to suppress redundant stimuli. Sensory gating (SG) refers to the attenuation of neural responses to the second identical stimulus in a paired-click paradigm, in which auditory stimuli are delivered in pairs with inter-stimulus intervals (ISI) of 500 ms and inter-pair intervals of 6–8 s. It is considered as an electrophysiological signal to reflect the brain’s automatic response to gate out repetitive sensory inputs. However, there has been no study systematically investigating SG function in aMCI patients. Thus, the present study used magnetoencephalography (MEG) to record neuromagnetic responses to a paired-click paradigm in 23 healthy controls (HC) and 26 aMCI patients. The Stimulus 2/Stimulus 1 (S2/S1) amplitude ratio was used to represent the SG function. Compared to HC, aMCI patients showed M50 SG deficits in the left inferior frontal gyrus (IFG) and right inferior parietal lobule (IPL). M100 SG defects were also observed in the right IPL. Based on the ROIs showing significant between-group SG differences, we found that a more deficient M50 SG function in the right IPL was associated with poorer performance in the immediate recall of Logic Memory (LM), Chinese Version Verbal Learning Test (CVVLT) and Digit Span Backward (DSB) Test. Furthermore, the M50 SG ratios of the right IPL together with the neuropsychological performance of LM and CVVLT demonstrated very good accuracy in the discrimination of aMCI from HC. In conclusion, compared to HC, aMCI patients showed a significant SG deficit in the right IPL, which was correlated with the auditory short-term memory function. We suggest the combination of SG in the right IPL, LM and CVVLT to be sensitive indicators to differentiate aMCI patients from HC.

Objectives: To compare habituation in auditory middle latency response (AMLR) to repetitive stimuli of vestibular migraine (VM) patients with Meniere's disease (MD) patients and healthy controls (HC) and to assess usefulness of AMLR for diagnosis of VM.Subjects: Thirteen unilateral definite MD patients (2 men, 11 women, mean age 50.6), 13 definite VM patients (3 men, 10 women, mean age 45.5), and 8 HC subjects (2 men, 6 women, mean age 37.1) were enrolled.Methods: The electrodes were placed on the vertex and the spinal process of the fifth cervical vertebra. Binaural click stimulation (0.1 ms, 70 dBnHL) was presented. A total of 800 responses were averaged. Averaged responses were divided into four sets (S1 to S4) according to the temporal order. No, Po, Na, and Pa were identified, and amplitudes and latencies were measured.Results: Concerning latencies, HC subjects showed a tendency of shorter latencies. However, there was no clear effect of repetitive stimulation. Concerning No-Po amplitudes, no significant differences were observed. Raw amplitudes of Na-Pa showed statistically significant differences in S1 and S2 among the groups (p < 0.01 one-way ANOVA). Differences were shown in MD vs. VM and HC vs. VM in S1 (smaller in VM) (p < 0.01 Bonferroni's test) and in MD vs. VM in S2 (smaller in VM) (p < 0.01 Bonferroni test). Relative amplitudes of Na-Pa to S1 showed statistically significant differences in S4 (p < 0.01 one-way ANOVA). Differences were shown in MD vs. VM and HC vs. VM (larger in VM) (p < 0.01 Bonferroni's test). Differences of Na-Pa amplitudes in S2 to S4 from Na-Pa amplitude in S1 were significant in S4 of VM patients (Dunnett's test).Conclusions: VM patients showed lack of habituation (potentiation) of Na-Pa amplitude in AMLR to repetitive stimuli while MD patients and HC subjects showed habituation. Observation of lack of habituation has high diagnostic accuracy for differential diagnosis of VM from MD.

Background: Altered sensorimotor gating has been demonstrated by Prepulse Inhibition (PPI) tests in patients with psychosis. Recent advances in signal processing methods allow assessment of neural PPI through electroencephalogram (EEG) recording during acoustic startle response measures (classic muscular PPI). Simultaneous measurements of muscular (eye-blink) and neural gating phenomena during PPI test may help to better understand sensorial processing dysfunctions in psychosis. In this study, we aimed to assess simultaneously muscular and neural PPI in early bipolar disorder and schizophrenia patients. Method: Participants were recruited from a population-based case-control study of first episode psychosis. PPI was measured using electromyography (EMG) and EEG in pulse alone and prepulse + pulse with intervals of 30, 60, and 120 ms in early bipolar disorder (n = 18) and schizophrenia (n = 11) patients. As control group, 15 socio-economically matched healthy subjects were recruited. All subjects were evaluated with Rating Scale, Hamilton Rating Scale for Depression, and Young Mania Rating Scale questionnaires at recruitment and just before PPI test. Wilcoxon ranked sum tests were used to compare PPI test results between groups. Results: In comparison to healthy participants, neural PPI was significantly reduced in PPI 30 and PPI60 among bipolar and schizophrenia patients, while muscular PPI was reduced in PPI60 and PPI120 intervals only among patients with schizophrenia. Conclusion: The combination of muscular and neural PPI evaluations suggested distinct impairment patterns among schizophrenia and bipolar disorder patients. Simultaneous recording may contribute with novel information in sensory gating investigations.

Abstract Background Childhood trauma (CT) has been found to contribute to the onset of schizophrenia and auditory sensory gating deficit is a leading endophenotype for schizophrenia. However, the association between the CT and sensory gating in first-episode schizophrenia remains elusive. Methods Fifty-six patients and 49 age and sex-matched healthy controls were assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) for CT and Positive and Negative Syndrome Scale (PANSS) for symptoms severity. Sensory gating was tested using the modified paradigm, perceived spatial separation-induced prepulse inhibition (PSS-PPI), and the perceived spatial co-location PPI (PSC-PPI or classical PPI). Results Comparing with healthy controls, the patients had significantly higher score on sexual abuse (t = 2.729, p

Background: Sensory gating refers to “filtering” of irrelevant sensory input in the brain. Auditory sensory gating deficit has been considered as a marker of schizophrenia (SCZ) and assessed using P50 paired-click paradigm. We explore sensory gating deficits and their clinical correlates in SCZ. Materials and Methods: Twenty-five drug-free/drug-naïve patients with SCZ, whose psychopathology was assessed using Positive and Negative Syndrome Scale (PANSS), and 25 age-matched normal controls (NC) were recruited. ERP recordings were done using 40-channel event-related potential measuring system. Results: S2-S1 P50 amplitude difference, an index of sensory gating, was significantly lower in SCZ at F3 and F4 sites when compared to NC, indicating impaired gating. SCZ had significantly lower S1 amplitude compared to NC at these sites; S2 amplitudes were comparable. The sensory gating index also showed significant correlations with PANSS scores. Conclusions: Our study reiterates sensory gating abnormalities in SCZ and confers a frontal specificity, implying specific deficits in early preattentive processes to them. Further, we suggest that gating deficits in SCZ are driven predominantly by abnormally small S1 rather than an inability to suppress S2. A correlation between sensory gating parameters and measures of psychopathology strengthens the hypothesis that abnormal response to sensory input may contribute to the psychopathology in SCZ.

Deficits in the gating of sensory stimuli, i.e., the ability to suppress the processing of irrelevant sensory input, are considered to play an important role in the pathogenesis of several neuropsychiatric disorders, in particular schizophrenia. Gating is disrupted both in schizophrenia patients and their unaffected relatives, suggesting that gating deficit may represent a biomarker associated with a genetic liability to the disorder. To assess the strength of the evidence for the etiopathogenetic links between genetic variation, gating efficiency, and schizophrenia, we carried out a systematic review of human genetic association studies of sensory gating (suppression of the P50 component of the auditory event-related brain potential) and sensorimotor gating (prepulse inhibition of the acoustic startle response). Sixty-three full-text articles met the eligibility criteria for inclusion in the review. In total, 117 genetic variants were reported to be associated with gating functions: 33 variants for sensory gating, 80 variants for sensorimotor gating, and four variants for both sensory and sensorimotor gating. However, only five of these associations (four for prepulse inhibition—CHRNA3 rs1317286, COMT rs4680, HTR2A rs6311, and TCF4 rs9960767, and one for P50 suppression—CHRNA7 rs67158670) were consistently replicated in independent samples. Although these variants and genes were all implicated in schizophrenia in research studies, only two polymorphisms (HTR2A rs6311 and TCF4 rs9960767) were also reported to be associated with schizophrenia at a meta-analytic or genome-wide level of evidence. Thus, although gating is widely considered as an important endophenotype of schizophrenia, these findings demonstrate that evidence for a common genetic etiology of impaired gating functions and schizophrenia is yet unsatisfactory, warranting further studies in this field. [ABSTRACT FROM AUTHOR]

Tourette syndrome (TS) is a neurodevelopmental disorder defined by tics, but most patients also experience bothersome sensory phenomena, in the form of premonitory urges and/or sensory hypersensitivity. Whereas premonitory urges are temporally paired with tics, sensory hypersensitivity is a constant, heightened awareness of external and/or internal stimuli. The intensity of sensory hypersensitivity does not strongly correlate with the severity of tics or premonitory urges, suggesting it is a dissociable clinical phenomenon. At least 80% of TS patients report subjectively enhanced perception of various sensory stimuli. These same patients demonstrate normal static detection thresholds. However, individuals with TS habituate abnormally to repetitive stimuli, indicating incapacity to appropriately filter redundant sensory input, i.e. impaired sensory gating. Physiologic support for this hypothesis is provided by abnormal pre-pulse inhibition (PPI) and event-related potential (ERP) investigations. Preclinical data implicates parvalbumin-positive (PV+) interneuron dysfunction in altered sensory gating in TS and other neurodevelopment disorders. Studies probing TS sensory hypersensitivity must methodically account for comorbid psychiatric conditions, namely obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), as these entities appear to involve pathophysiologic processes shared with TS. The presence of psychiatric comorbidities in TS is associated with even more profound sensory processing dysfunction. A deepened understanding of TS sensory hypersensitivity will afford novel insights into disease mechanisms, clinical phenotype, and therapeutic management. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence views hypertension as a stress-induced disorder. Stressors must be "gated" by the brain before any inflammatory or immune processes that contribute to hypertension are initiated. No studies were found that examined sensory gating in relation to hypertension. Objectives: The aim of the study was to determine if disturbances in self-reported sensory gating could differentiate normotensive from hypertensive young adults. Methods: A nonmatched, case--control design was used. We administered an online survey to 163 young adult participants. Participants were predominantly female, in their mid-20s, well educated, and approximately evenly distributed by race and hypertension status. The Sensory Gating Inventory (SGI) measured gating disturbances. Results: The mean SGI scores were significantly higher among persons diagnosed with hypertension, reflecting a moderate effect size of sensory gating. After adjusting for confounders, however, the normotensive and hypertensive groups were not significantly different on their SGI scores. Discussion: With an observed moderate effect size of 0.35, but low power, more research is warranted regarding the role of gating disturbances in the development of stress-induced hypertension. Clinically, the SGI may be important for screening patients who would benefit from ambulatory blood pressure monitoring to identify persons with masked hypertension. [ABSTRACT FROM AUTHOR]

Modulating cortical excitability based on a stimulus' relevance to the task at hand is a component of sensory gating, and serves to protect higher cortical centers from being overwhelmed with irrelevant information (McIlroy et al., 2003; Kumar et al., 2005; Wasaka et al., 2005). This study examined relevancy-based modulation of cortical excitability, and corresponding behavioral responses, in the face of distracting stimuli in participants with and without a history of concussion (mean age 22 ± 3 SD years; most recent concussion 39.1 ± 30 SD months). Participants were required to make a scaled motor response to the amplitudes of visual and tactile stimuli presented individually or concurrently. Task relevance was manipulated, and stimuli were occasionally presented with irrelevant distractors. Electroencephalography (EEG) and task accuracy data were collected from participants with and without a history of concussion. The somatosensory-evoked N70 event-related potential (ERP) was significantly modulated by task relevance in the control group but not in those with a history of concussion, and there was a significantly greater cost to task accuracy in the concussion history group when relevant stimuli were presented with an irrelevant distractor. This study demonstrated that relevancy-based modulation of electrophysiological responses and behavioral correlates of sensory gating differ in people with and without a history of concussion, even after patients were symptom-free and considered recovered from their injuries. [ABSTRACT FROM AUTHOR]

Background: Somatosensory temporal discrimination threshold (STDT) is altered in multiple sclerosis (MS). In healthy subjects (HS), voluntary movement modulates the STDT through mechanisms of subcortical sensory gating. Objective: With neurophysiological and magnetic resonance imaging (MRI) techniques, we investigated sensory gating and sensorimotor integration in MS. Methods: We recruited 38 relapsing-remitting multiple sclerosis (RR-MS) patients with no-to-mild disability and 33 HS. We tested STDT at rest and during index finger abductions and recorded the movement kinematics. Participants underwent a 3T MRI protocol. Results: Patients exhibited higher STDT values and performed slower finger movements than HS. During voluntary movement, STDT values increased in both groups, albeit to a lesser extent in patients, while the mean angular velocity of finger movements decreased in patients alone. Patients had a smaller volume of the thalamus, pallidum and caudate nucleus, and displayed higher mean diffusivity in the putamen, pallidum and thalamus. STDT correlated with thalamic volume while mean angular velocity correlated with putaminal volume. Changes in mean angular velocity during sensorimotor integration inversely correlated with mean diffusivity in the thalamus and pallidum. Changes in STDT and velocity were associated with fatigue score. Conclusion: Altered STDT and sensorimotor integration are related to structural damage in the thalamus and basal ganglia in MS and likely to affect motor performance. [ABSTRACT FROM AUTHOR]

Introduction: Inhibitory sensory gating of the P50 cerebral evoked potential to paired auditory stimuli (S1, S2) is a widely used paradigm for the study of schizophrenia and related conditions. Its use to measure genetic, treatment, and developmental effects requires a metric with more stable properties than the simple ratio of the paired responses.Methods: This study assessed the ratio P50S2μV/P50S1μV and P50S2μV co-varied for P50S1μV in all 27 independent published studies that compared schizophrenia patients with healthy controls from 2000 to 2019. The largest study from each research group was selected. The Colorado research group's studies were excluded to eliminate bias from the first report of the phenomenon.Results: Across the 27 studies encompassing 1179 schizophrenia patients and 1091 healthy controls, both P50S2μV co-varied for P50S1μV and P50S2μV/P50S1μV significantly separated the patients from the controls (both P < 0.0001). Effect size for P50S2μV co-varied for P50S1μV is d' = 1.23. The normal distribution of P50S2μV co-varied for P50S1μV detected influences of maternal inflammation and effects on behavior in a recent developmental study, an emerging use for the P50 inhibitory gating measure. P50S2μV/P50S1μV was not normally distributed. Results from two multi-site NIMH genetics collaborations also support the use of P50S2μV as a biomarker.Conclusion: Both methods detect an abnormality of cerebral inhibition in schizophrenia with high significance across multiple independent laboratories. The normal distribution of P50S2μV co-varied for P50S1μV makes it more suitable for studies of genetic, treatment, and other influences on the development and expression of inhibitory deficits in schizophrenia. [ABSTRACT FROM AUTHOR]

Measures of the brain's automatic electrophysiological responses to sounds represent a potential tool for identifying age- and depression-related neural markers. However, these markers have rarely been studied related to aging and depression within one study. Here, we investigated auditory event-related potentials (ERPs) in the brain that may show different alterations related to aging and depression. We used an oddball condition employing changes in sound intensity to investigate: (i) sound intensity dependence; (ii) sensory gating; and (iii) change detection, all within a single paradigm. The ERPs of younger (18–40 years) and older (62–80 years) depressed female participants and age-matched non-depressed participants were measured. Intensity dependence was examined as the difference between N1 responses to repeated high- and low-intensity sounds, sensory gating as N1 responses to rare and repeated sounds, and change detection as indexed by the mismatch negativity (MMN). We found that intensity dependence was greater in older participants than younger ones, indicating effects related to aging but not to depression. For sensory gating, we found depression- and age-related alterations as increased N1 responses. No group differences were found for MMN. Although a sensory gating deficit was expected in older adults, this study is the first to demonstrate age-related overexcitability in sound intensity dependency. The results indicate that automatic brain responses to sound intensity changes are suitable for studying age- and depression-related neural markers but may not be sensitive enough to differentiate the effects of aging and depression. [ABSTRACT FROM AUTHOR]

• We compared cognition and P50 sensory gating in 38 schizophrenia and 32 controls. • Patients showed higher P50 gating ratio and S2 amplitude but lower S1 amplitude. • S1 or S2 amplitude was possibly correlated with some cognitive domains in patients. Cognitive deficits are core symptoms of schizophrenia; however, their pathophysiological mechanisms are still unclear. A sensory gating deficit, as reflected by P50 suppression, has been repeatedly shown in schizophrenia patients, which may be associated with cognitive deficits in this disorder. The present study was to examine the relationship between the P50 suppression and cognitive deficits in patients with schizophrenia, which is still under-investigated. We recruited 38 chronic schizophrenia patients and 32 matched healthy controls, and assessed their cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and P50 suppression with the electroencephalography system. The total and its 4 index scores (all p < 0.05) except for the visuospatial/ constructional index of RBANS were significantly lower in patients compared with healthy controls. However, only the language and attention passed Bonferroni corrections. Patients displayed a significantly higher P50 ratio, higher S2 amplitude, and lower S1 amplitude (all p < 0.05) than healthy controls. Interestingly, only in the patients, the S1 amplitude was associated with both language and attention, and the S2 amplitude with both visuospatial/ constructional and language (all p < 0.05), although all of these significances did not pass the Bonferroni corrections. The P50 ratio was not associated with any of the RBANS scores (all p > 0.05). Our results suggest the P50 suppression deficits in Chinese patients with schizophrenia, which may be associated with cognitive impairments of this illness. Moreover, the amplitude of S1 and the amplitude of S2 may be involved in the different cognitive domain deficits in schizophrenia patients. This study suggests that the P50 components may possibly be effective biomarkers for cognitive deficits in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Objectives: To compare habituation in auditory middle latency response (AMLR) to repetitive stimuli of vestibular migraine (VM) patients with Meniere's disease (MD) patients and healthy controls (HC) and to assess usefulness of AMLR for diagnosis of VM. Subjects: Thirteen unilateral definite MD patients (2 men, 11 women, mean age 50.6), 13 definite VM patients (3 men, 10 women, mean age 45.5), and 8 HC subjects (2 men, 6 women, mean age 37.1) were enrolled. Methods: The electrodes were placed on the vertex and the spinal process of the fifth cervical vertebra. Binaural click stimulation (0.1 ms, 70 dBnHL) was presented. A total of 800 responses were averaged. Averaged responses were divided into four sets (S1 to S4) according to the temporal order. No, Po, Na, and Pa were identified, and amplitudes and latencies were measured. Results: Concerning latencies, HC subjects showed a tendency of shorter latencies. However, there was no clear effect of repetitive stimulation. Concerning No-Po amplitudes, no significant differences were observed. Raw amplitudes of Na-Pa showed statistically significant differences in S1 and S2 among the groups (p < 0.01 one-way ANOVA). Differences were shown in MD vs. VM and HC vs. VM in S1 (smaller in VM) (p < 0.01 Bonferroni's test) and in MD vs. VM in S2 (smaller in VM) (p < 0.01 Bonferroni test). Relative amplitudes of Na-Pa to S1 showed statistically significant differences in S4 (p < 0.01 one-way ANOVA). Differences were shown in MD vs. VM and HC vs. VM (larger in VM) (p < 0.01 Bonferroni's test). Differences of Na-Pa amplitudes in S2 to S4 from Na-Pa amplitude in S1 were significant in S4 of VM patients (Dunnett's test). Conclusions: VM patients showed lack of habituation (potentiation) of Na-Pa amplitude in AMLR to repetitive stimuli while MD patients and HC subjects showed habituation. Observation of lack of habituation has high diagnostic accuracy for differential diagnosis of VM from MD. [ABSTRACT FROM AUTHOR]

Studies of central auditory processing underlying speech‐in‐noise (SIN) recognition in aging have mainly concerned the degrading neural representation of speech sound in the auditory brainstem and cortex. Less attention has been paid to the aging‐related decline of inhibitory function, which reduces the ability to suppress distraction from irrelevant sensory input. In a response suppression paradigm, young and older adults listened to sequences of three short sounds during MEG recording. The amplitudes of the cortical P30 response and the 40‐Hz transient gamma response were compared with age, hearing loss and SIN performance. Sensory gating, indicated by the P30 amplitude ratio between the last and the first responses, was reduced in older compared to young listeners. Sensory gating was correlated with age in the older adults but not with hearing loss nor with SIN understanding. The transient gamma response expressed less response suppression. However, the gamma amplitude increased with age and SIN loss. Comparisons of linear multi‐variable modeling showed a stronger brain–behavior relationship between the gamma amplitude and SIN performance than between gamma and age or hearing loss. The findings support the hypothesis that aging‐related changes in the balance between inhibitory and excitatory neural mechanisms modify the generation of gamma oscillations, which impacts on perceptual binding and consequently on SIN understanding abilities. In conclusion, SIN recognition in older age is less affected by central auditory processing at the level of sensation, indicated by sensory gating, but is strongly affected at the level of perceptual organization, indicated by the correlation with the gamma responses. [ABSTRACT FROM AUTHOR]

Objective: Cognitive impairment is a core symptom of schizophrenia (SCZ); however, its pathophysiological mechanisms remain unclear. The sensory gating (SG) deficits reflected by P50 inhibition are recurring in SCZ, and this inhibition may be related to the cognitive deficits seen in these individuals. This study aimed to investigate the relationship between P50 inhibition and cognitive dysfunction in SCZ, which has not been fully investigated up to this point.Methods: A total of 270 individuals with chronic SCZ and 116 healthy controls were enrolled in the study. Psychopathology of SCZ was rated by the positive and negative syndrome scale (PANSS), while cognitive function and P50 inhibition of subjects were assessed by the MATRICS Consensus Cognitive Battery (MCCB) and the electroencephalography system.Results: The MCCB total and its 10 index scores were significantly lower in patients than those in healthy controls (all p < 0.001). SCZ patients had a lower amplitude of S1, and higher P50 ratio than healthy controls (both p < 0.01). However, there were no significant correlations between the P50 ratio and any of the PANSS total and its subscale scores in SCZ patients (all p > 0.05). Moreover, no correlation was found between the P50 components and the MCCB scores (all p > 0.05).Conclusions: Our findings suggest that the P50 inhibition deficits occur in Chinese individuals with SCZ, which may not be associated with their clinical symptoms and cognitive impairment. [ABSTRACT FROM AUTHOR]

Objective: Despite its numerous side effects, clozapine is still the most effective antipsychotics making it an ideal reference substance to validate the efficacy of novel compounds for the treatment of schizophrenia. However, blood–brain barrier permeability for most new molecular entities is unknown, requiring central delivery. Thus, we performed a dose-finding study for chronic intracerebroventricular (icv) delivery of clozapine in mice. Methods: Specifically, we implanted wild-type C57BL/6J mice with osmotic minipumps (Alzet) delivering clozapine at a rate of 0.15 µl/h at different concentrations (0, 3.5, 7 and 14 mg/ml, i.e. 0, 12.5, 25 and 50 µg/day). Mice were tested weekly in a modified SHIRPA paradigm, for locomotor activity in the open field and for prepulse inhibition (PPI) of the acoustic startle response (ASR) for a period of 3 weeks. Results: None of the clozapine concentrations caused neurological deficits or evident gross behavioural alterations in the SHIRPA paradigm. In male mice, clozapine had no significant effect on locomotor activity or PPI of the ASR. In female mice, the 7 and 14 mg/ml dose of clozapine significantly affected both open field activity and PPI, while 3.5 mg/ml of clozapine increased PPI but had no effects on locomotor activity. Conclusion: Our findings indicate that 7 mg/ml may be the optimal dose for chronic icv delivery of clozapine in mice, allowing comparison to screen for novel antipsychotic compounds. [ABSTRACT FROM AUTHOR]

Reduced prepulse inhibition (PPI) of startle provides evidence of deficient sensorimotor gating in several disorders, including schizophrenia. The role of NMDA neurotransmission in the regulation of PPI is unclear, due to cross-species differences in the effects of NMDA antagonists on PPI. Recent reports suggest that drug effects on PPI differ in subgroups of normal humans that differ in the levels of baseline PPI or specific personality domains; here, we tested the effects of these variables on the sensitivity of PPI to the NMDA antagonist, memantine. PPI was measured in male Sprague-Dawley rats, after treatment with memantine (0, 10 or 20 mg/kg, s.c.). Baseline PPI was then measured in 37 healthy adult men. Next, subjects were tested twice, in a double-blind crossover design, comparing either (1) placebo vs 20 mg of the NMDA antagonist memantine (n=19) or (2) placebo vs 30 mg memantine (n=18). Tests included measures of acoustic startle amplitude, PPI, autonomic indices and subjective self-rating scales. Memantine had dose- and interval-dependent effects on PPI in rats. Compared with vehicle, 10 mg/kg increased short-interval (10-20 ms) PPI, and 20 mg/kg decreased long-interval (120 ms) PPI. In humans, memantine caused dose-dependent effects on psychological and somatic measures: 20 mg was associated with increased ratings of happiness, and 30 mg was associated with increased ratings of dizziness. PPI at the 120 ms prepulse interval was increased by 20 mg, but not 30 mg of memantine. Subgroups most sensitive to the PPI-enhancing effects of memantine were those with low baseline PPI, or with personality scale scores suggestive of high novelty seeking, high sensation seeking, or high disinhibition. NMDA blockade with memantine appears to have dose- and interval-dependent effects on sensorimotor gating in rats and humans, particularly among specific subgroups of normal human subjects. These findings are discussed as they relate to consistencies across other studies in humans, as well as apparent inconsistencies in the NMDA regulation of PPI across species.

The Sp4 transcription factor plays a critical role for both development and function of mouse hippocampus. Reduced expression of the mouse Sp4 gene results in a variety of behavioral abnormalities relevant to human psychiatric disorders. The human SP4 gene is therefore examined for its association with both bipolar disorder and schizophrenia in European Caucasian and Chinese populations respectively. Out of ten SNPs selected from human SP4 genomic locus, four displayed significant association with bipolar disorder in European Caucasian families (rs12668354, p = 0.022; rs12673091, p = 0.0005; rs3735440, p = 0.019; rs11974306, p = 0.018). To replicate the genetic association, the same set of SNPs was examined in a Chinese bipolar case control sample. Four SNPs displayed significant association (rs40245, p = 0.009; rs12673091, p = 0.002; rs1018954, p = 0.001; rs3735440, p = 0.029), and two of them (rs12673091, rs3735440) were shared with positive SNPs from European Caucasian families. Considering the genetic overlap between bipolar disorder and schizophrenia, we extended our studies in Chinese trios families for schizophrenia. The SNP7 (rs12673091, p = 0.012) also displayed a significant association. The SNP7 (rs12673091) was therefore significantly associated in all three samples, and shared the same susceptibility allele (A) across all three samples. On the other hand, we found a gene dosage effect for mouse Sp4 gene in the modulation of sensorimotor gating, a putative endophenotype for both schizophrenia and bipolar disorder. The deficient sensorimotor gating in Sp4 hypomorphic mice was partially reversed by the administration of dopamine D2 antagonist or mood stabilizers. Both human genetic and mouse pharmacogenetic studies support Sp4 gene as a susceptibility gene for bipolar disorder or schizophrenia. The studies on the role of Sp4 gene in hippocampal development may provide novel insights for the contribution of hippocampal abnormalities in these psychiatric disorders.

Many studies have found that the P50 sensory gating ratio in a paired click task is smaller in normal control subjects than in patients with schizophrenia, indicating more effective sensory gating. However, a wide range of gating ratios has been reported in the literature for both groups. The purpose of this study was to compile these findings and to compare reported P50 gating ratios in controls and patients with schizophrenia. Current data collected from individual controls in eight studies from the University of California, Irvine (UCI), Indiana University (IU), and Yale University also are reported. The IU, UCI, and Yale data showed that approximately 40% of controls had P50 ratios within 1 S.D. below the mean of means for patients with schizophrenia. The meta-analysis rejected the null hypothesis that all studies showed no effect. The meta-analysis also showed that the differences were not the same across all studies. The mean ratios in 45 of the 46 group comparisons were smaller for controls than for patients, and the observed difference in means was significant for 35 of those studies. Reported gating ratios for controls from two laboratories whose findings were reported in the literature differed from all the other control groups. Variables affecting the gating ratio included band pass filter setting, rules regarding the inclusion of P30, sex, and age. Standards of P50 collection and measurement would help determine whether the gating ratio can be sufficiently reliable to be labeled an endophenotype, and suggestions are made toward this goal.

The complexity change in brain activity in schizophrenia is an interesting topic clinically. Schizophrenia patients exhibit abnormal task-related modulation of complexity, following entropy of electroencephalogram (EEG) analysis. However, complexity modulation in schizophrenia patients during the sensory gating (SG) task, remains unknown. In this study, the classical auditory paired-stimulus paradigm was introduced to investigate SG, and EEG data were recorded from 55 normal controls and 61 schizophrenia patients. Fuzzy entropy (FuzzyEn) was used to explore the complexity of brain activity under the conditions of baseline (BL) and the auditory paired-stimulus paradigm (S1 and S2). Generally, schizophrenia patients showed significantly higher FuzzyEn values in the frontal and occipital regions of interest (ROIs). Relative to the BL condition, the normalized values of FuzzyEn of normal controls were decreased greatly in condition S1 and showed less variance in condition S2. Schizophrenia patients showed a smaller decrease in the normalized values in condition S1. Moreover, schizophrenia patients showed significant diminution in the suppression ratios of FuzzyEn, attributed to the higher FuzzyEn values in condition S1. These results suggested that entropy modulation during the process of sensory information and SG was obvious in normal controls and significantly deficient in schizophrenia patients. Additionally, the FuzzyEn values measured in the frontal ROI were positively correlated with positive scores of Positive and Negative Syndrome Scale (PANSS), indicating that frontal entropy was a potential indicator in evaluating the clinical symptoms. However, negative associations were found between the FuzzyEn values of occipital ROIs and general and total scores of PANSS, likely reflecting the compensation effect in visual processing. Thus, our findings provided a deeper understanding of the deficits in sensory information processing and SG, which contribute to cognitive deficits and symptoms in patients with schizophrenia.

Genome-wide association studies (GWASs) have reported multiple single nucleotide polymorphisms (SNPs) associated with schizophrenia, yet the underlying molecular mechanisms are largely unknown. In this study, we aimed to identify schizophrenia relevant genes showing alterations in mRNA and protein expression associated with risk SNPs at the 10q24.32-33 GWAS locus. We carried out the quantitative trait loci (QTL) and summary data-based Mendelian randomization (SMR) analyses, using the PsychENCODE dorsolateral prefrontal cortex (DLPFC) expression QTL (eQTL) database, as well as the ROSMAP and Banner DLPFC protein QTL (pQTL) datasets. The gene CNNM2 (encoding a magnesium transporter) at 10q24.32-33 was identified to be a robust schizophrenia risk gene, and was highly expressed in human neurons according to single cell RNA-seq (scRNA-seq) data. We further revealed that reduced Cnnm2 in the mPFC of mice led to impaired cognition and compromised sensorimotor gating function, and decreased Cnnm2 in primary cortical neurons altered dendritic spine morphogenesis, confirming the link between CNNM2 and endophenotypes of schizophrenia. Proteomics analyses showed that reduced Cnnm2 level changed expression of proteins associated with neuronal structure and function. Together, these results identify a robust gene in the pathogenesis of schizophrenia., (© 2023. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Purpose: Sensory gating is the cortical phenomenon that involves selective inhibition of responses to task-irrelevant stimuli. Perceiving speech in noise, a situation commonly encountered by humans, requires the irrelevant noise to be inhibited while processing the relevant speech stimulus. We hypothesized that the two (sensory gating and speech perception in noise [SPiN]) might be related and that sensory gating may provide evidence of cortical inhibition involved in SPiN., Method: An observational research following a correlational design was conducted on 10 neurotypical individuals. Auditory sensory gating was assessed using a conditioning-testing paradigm for tone and speech token pairs. The SPiN was measured using standardized sentences in the participants' native language., Results: Differences were observed in the gating index of the P2 peaks of speech and tone pairs. A significant relationship between SPiN and the auditory sensory gating of the P2 peak of the speech-evoked cortical potential was obtained., Conclusion: The results of this preliminary investigation indicate an association between the sensory gating mechanism and neurotypical individuals' ability to perceive speech in noise.

Clinical descriptions of perceptual and attentional anomalies in schizophrenia emphasize phenomena such as flooding, or inundation, by sensory stimuli. A failure of sensory "gating" mechanisms in the brain is hypothesized to account for these symptoms, and this hypothesis has led to a marked interest in their putative psychophysiological substrates. However, there are no systematic analyses of the phenomenology of these perceptual experiences, nor has the hypothesized connection between the clinical phenomena and their reported psychophysiological substrates been tested. In this investigation, a structured interview instrument was developed to measure perceptual anomalies as distinct from hallucinations and to determine their prevalence across sensory modalities in schizophrenia in 67 schizophrenia subjects and 98 normal controls. The instrument includes Likert ratings of hypersensitivity, inundation, and selective attention to external sensory stimuli. Good interrater agreement, determined from interviews, was obtained. Schizophrenia subjects had significantly higher auditory, visual, and combined scores (i.e., across all modalities) than normal controls did, indicating significantly more perceptual anomalies. For the schizophrenia group, the prevalence of auditory and visual anomalies was significantly greater than the other sensory modalities. The data indicate that the putative phenomenological correlates of sensory gating may be reliably measured and tested with the Structured Interview for Assessing Perceptual Anomalies.

Background: Some tinnitus participants habituate to their tinnitus, but some others do not and complain of its annoyance so much. It has been suggested that tinnitus is a habituation deficit. Habituation and the ability to ignore a sensory input depend on the normal function of filtering mechanism of sensory gating. Purpose: The purpose of this study was to compare behavioral aspects of sensory gating in normal and tinnitus participants to search for the reason why some tinnitus participants habituate to their tinnitus but some others do not. Research Design: This investigation was an observational case--control study. Study Sample: There were 60 tinnitus participants who were categorized into two tinnitus groups (30 compensated tinnitus participants and 30 decompensated tinnitus participants) based on the complaint of tinnitus annoyance, visual analog scale (VAS) for tinnitus loudness, annoyance, and awareness, scores on Tinnitus Questionnaire (TQ), and Tinnitus Handicap Inventory (THI). Also, there were 30 normal hearing participants without tinnitus as the normal control group. Data Collection and Analysis: Sensory Gating Inventory (SGI), TQ, THI, and VAS was obtained from all participants. THI, TQ, VAS, and SGI total scores and their factors were compared among the groups. Correlations between SGI scores with THI, TQ, and VAS score were calculated. Results: The results showed that SGI total score and the scores of its four factors were significantly higher in decompensated tinnitus participants compared with compensated tinnitus participants and normal controls. Also, there was a positive correlation between SGI perceptual modulation factor and TQ emotional distress factor and with the VAS for loudness in decompensated tinnitus group. Conclusions: These results suggested that tinnitus associated with behavioral aspects of sensory gating and decompensated tinnitus may be a result of deficient sensory gating. [ABSTRACT FROM AUTHOR]

Objectives Considering the common neurological origins, there is a relationship between the sensory gating and cognitive functions. However, there is no adequate information on this issue. In this study, auditory event-related potentials and the sensory gating performance were assessed in P50, N100 and P200 waves. Besides, their relationship with cognitive performance in auditory and visual modalities was investigated. Materials & Methods Nineteen normal primary school students (14 boys) were tested in Tehran, Iran from 2017 to 2018. In the auditory modality, the Persian version of the non-word repetition test and monaural selective auditory attention test (mSAAT) were used for assessment of the working memory and selective attention, respectively. In order to evaluate the visual working memory and visual selective attention, Rey-Osterrieth complex figure, selective and divided attention test were used, respectively. A 32-channel EEG system was used for electrophysiological assessment. Results The P50 sensory gating was negatively correlated with the visual selective attention (P=0.034, r=-0.49) and N100 sensory gating was negatively correlated with the auditory working memory (P=0.043, r=-0.48) as well as visual selective attention (P=0.039, r=-0.47). For P200, there was a significant negative relationship with auditory selective attention in the right ear (P=0.034, r=-0.49). Conclusion Sensory gating in children is not a modality-specific phenomenon. Sensory gating in a modality could be associated with cognitive functions in other modalities. [ABSTRACT FROM AUTHOR]

Paired-pulse suppression refers to attenuation of neural activity in response to a second stimulus and has a pivotal role in inhibition of redundant sensory inputs. Previous studies have suggested that cortical responses to a somatosensory stimulus are modulated not only by a preceding same stimulus, but also by stimulus from a different submodality. Using magnetoencephalography, we examined somatosensory suppression induced by three different conditioning stimuli. The test stimulus was a train of electrical pulses to the dorsum of the left hand at 100 Hz lasting 1500 ms. For the pulse train, the intensity of the stimulus was abruptly increased at 1200 ms. Cortical responses to the abrupt intensity change were recorded and used as the test response. Conditioning stimuli were presented at 600 ms as pure tones, either innocuous or noxious electrical stimulation to the right foot. Four stimulus conditions were used: (1) Test alone, (2) Test + auditory stimulus, (3) Test + somatosensory stimulus, and (4) Test + nociceptive stimulus. Our results showed that the amplitude of the test response was significantly smaller for conditions (3) and (4) in the secondary somatosensory cortex contralateral (cSII) and ipsilateral (iSII) to the stimulated side as compared to the response to condition (1), whereas the amplitude of the response in the primary somatosensory cortex did not differ among the conditions. The auditory stimulus did not have effects on somatosensory change-related response. These findings show that somatosensory suppression was induced by not only a conditioning stimulus of the same somatosensory submodality and the same cutaneous site to the test stimulus, but also by that of a different submodality in a remote area. [ABSTRACT FROM AUTHOR]

Objective: The inability to filter sensory input correctly may impair higher cognitive function in ADHD. However, this relationship remains largely elusive. The objectives of the present study is to investigate the relationship between sensory input processing and cognitive function in adult patients with ADHD. Method: This study investigated the relationship between deficit in sensory gating capacity (P50 amplitude changes in a double-click conditioning-testing paradigm and perceptual abnormalities related to sensory gating deficit with the Sensory Gating Inventory [SGI]) and attentional and executive function (P300 amplitude in an oddball paradigm and attentional and executive performances with a neuropsychological test) in 24 adult patients with ADHD. Results: The lower the sensory gating capacity of the brain and the higher the distractibility related to sensory gating inability that the patients reported, the lower the P300 amplitude. Conclusion: The capacity of the brain to gate the response to irrelevant incoming sensory input may be a fundamental protective mechanism that prevents the flooding of higher brain structures with irrelevant information in adult patients with ADHD. [ABSTRACT FROM AUTHOR]

Schizotypy is a personality dimension within the general population elevated among schizophrenia-spectrum patients and their first-degree relatives. Sensory gating is the pre-attentional habituation of responses distinguishing between important and irrelevant information. This is measured by event-related potentials, which have been found to display abnormalities in schizophrenic disorders. The current study investigated whether 6-month-old infants of mothers with schizotypic traits display sensory gating abnormalities. The paired-tone paradigm: two identical auditory tones (stimulus 1 and stimulus 2) played 500 ms apart, was used to probe the selective activation of the brain during 15-minutes of sleep. Their mothers completed the Oxford and Liverpool Inventory of Feelings and Experiences-Short Form as an index of schizotypy dimensionality, categorized into: infants of control, and infants of schizotypic, mothers. The findings revealed that although the infants' P50 components displayed significant differences between stimulus 1 and stimulus 2 in the paired-tone paradigm, there was no clear difference between infants of schizotypic and infants of control mothers. In contrast, all mothers displayed significant differences between stimulus 1 and stimulus 2, as observed in the infants, but also significant differences between their sensory gating ability correlated with schizotypy dimensionality. These findings are consistent with sensory processes, such as sensory gating, evidencing impairment in schizophrenia-spectrum disorders. The present research supports the idea that first-degree relatives of individuals who identify on this spectrum, within the sub-clinical category, do not display the same deficit at 6 postnatal months of age. [ABSTRACT FROM AUTHOR]

• Neural correlates of sensory gating (SG) deficits in PD are poorly understood. • We used paired-click paradigm and MEG imaging to study SG function in STG and IFG. • PD patients showed declined SG function in right STG and right IFG. • SG of the right IFG was correlated with somatic symptoms and distractibility. • We suggest PD patients showed reduced ability to filter out irrelevant information. Patients with panic disorder (PD) exhibit abnormalities in early-stage information processing, even for the nonthreatening stimuli. A previous event-related potential study reported that PD patients show a deficit in sensory gating (SG), a protective mechanism of the brain to filter out irrelevant sensory inputs. However, there is no clear understanding about the neural correlates of SG deficits in PD. Moreover, whether SG deficits, if any, are associated with clinical manifestations remain unknown. In this study, 18 patients with PD and 20 age- and gender-matched healthy controls were recruited to perform auditory paired-stimulus paradigm using magnetoencephalographic (MEG) recordings. Results showed that PD patients demonstrated significantly higher M50 SG ratios in the right inferior frontal gyrus (RIFG) and higher M100 SG ratios in both RIFG and right superior temporal gyrus (RSTG) than those of the control group. It was important to note that in the RIFG, the M50 SG ratios correlated significantly with the scores of Body Sensation Questionnaire (BSQ) and Distractibility scale of Sensory Gating Inventory among patients with PD. In conclusion, this study suggests that PD patients exhibited a deficient ability to filter out irrelevant information, and such a defect might lead to cognitive misinterpretation of somatic sensations and distractibility. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia (SCZ) patients and relatives have deficits in early cortical sensory gating (SG) typically measured by suppression of electroencephalography-derived P50 event-related potentials (ERPs) in a conditioning-testing (S1-S2) paradigm. Associated with alpha 7 nicotinic acetylcholine receptor (α7 nAChR) dysfunction and shown to be improved with nicotine and α7 nAChR agonists, SG has recently been shown to be improved in low P50 suppressing SCZ patients following acute CDP-choline treatment.Aims: This pilot study in healthy humans assessed the SG effects of an α7 nAChR strategy combining CDP-choline with galantamine, a positive allosteric modulator (PAM) of nAChRs, aimed at increasing and prolonging nicotinic receptor activity.Methods: The combined effect of CDP-choline (500 mg) and galantamine (16 mg) on speech P50 gating indices rP50 (S2/S1) and dP50 (S1-S2) was examined in 30 healthy participants stratified into low and high baseline P50 suppressors in a randomized, double-blind, placebo-controlled and counterbalanced design.Results: In low suppressors, CDP-choline/galantamine (vs. placebo) improved rP50 and dP50 gating, and reduced S2P50 amplitudes. No P50 gating effects were observed in high suppressors; however, CDP-choline/galantamine (vs. placebo) increased their S2P50 amplitudes.Conclusion: Findings from this pilot study with CDP-choline/galantamine in a healthy, SCZ-like surrogate deficient gating sample are consistent with the association of α7 nAChR mechanisms in SG impairment in SCZ and support further research trials with CDP-choline and galantamine targeting sensory processes. [ABSTRACT FROM AUTHOR]

The effects of the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene on sensory gating were studied in 41 mentally healthy volunteers (healthy group) and 39 patients with schizophrenia. P50 auditory event-related potentials obtained in the paired-pulse stimulation paradigm with an interpulse interval of 500 msec were recorded. Comparison of the two groups demonstrated a decrease in P50 inhibition in patients as compared with the healthy group (p < 0.05). The COMT polymorphism was found to affect the parameters of the P50 wave only in the healthy group: carriers of the Val/Val genotype had maximum-amplitude responses to the first stimulus in the pair (A1) and the highest level of inhibition of P50. Comparison of measures of P50 inhibition between the healthy and schizophrenia groups with different variants of the Val158Met genotype revealed significant differences only in comparison with the cohort with the Val/Val genotype. P50 latency was significantly influenced by the genotype factor in the combined cohort of healthy volunteers and patients, due to an increase in latency in carriers of the Met/Met genotype. In the patients group, the profile of correlations between P50 parameters and the PANSS was found to depend on the COMT genotype. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia affects approximately 10% of the world's population. Early detection of schizophrenia may significantly delay its progression. Although sensory gating deficits are reported in schizophrenia, it remains challenging how sensory gating deficits can be used with other metrics for risk detection and early diagnosis. Research design and methods: Using EEG, the authors examined effects of sensory gating on the performance of 136 participants in a P50 sensory gating task, including patients with first-episode schizophrenia (FESZ), ultra-high risk (UHR) individuals, high-risk (HR) individuals, and age- and sex-matched healthy controls (HCs). The authors also explored the differences among all groups using clinical assessments and cognitive tests. Results: Compared with HCs, HR, UHR and FESZ groups showed significant P50 suppression impairment. Furthermore, EEG source localization analyses identified successively stronger activation in prefrontal and anterior temporal regions in the HR, UHR and FESZ groups than in the HC group. Moreover, brain connectivity (HC < HR < UHR < FESZ) in the gamma band of P50 components was increasingly enhanced in accordance with the level of psychosis risks. Conclusions: These findings suggest that EEG source imaging techniques, brain network dynamics, and behavioral tests, can help clearly distinguish different stages of schizophrenia, and may assist in the early diagnosis of schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract Sensory gating, the ability to suppress sensory information of irrelevant stimuli, is affected in several neuropsychiatric diseases, notably schizophrenia and autism. It is currently unclear how these deficits interact with other hallmark symptoms of these disorders, such as social withdrawal and difficulty with interpersonal relationships. The highly affiliative prairie vole (Microtus ochrogaster) may be an ideal model organism to study the neurobiology underlying social behavior. In this study, we assessed unimodal acoustic sensory gating in male and female prairie voles using the prepulse inhibition (PPI) paradigm, whereby a lower amplitude sound (prepulse) decreases the startle response to a high amplitude sound (pulse) compared to the high amplitude sound alone. Prairie voles showed evidence of PPI at all prepulse levels compared to pulse alone, with both males and females showing similar levels of inhibition. However, unlike what has been reported in other rodent species, prairie voles did not show a within-session decrease in startle response to the pulse alone, nor did they show a decrease in startle response to the pulse over multiple days, highlighting their inability to habituate to startling stimuli (short- and long-term). When contrasted with a cohort of male wildtype C57Bl/6J mice that underwent a comparable PPI protocol, individual voles showed significantly higher trial-by-trial variability as well as longer latency to startle than mice. The benefits and caveats to using prairie voles in future sensory gating experiments are discussed. [ABSTRACT FROM AUTHOR]

Background: Impairments in mechanisms underlying early information processing have been reported in posttraumatic stress disorder (PTSD); however, findings in the existing literature are inconsistent. This current study capitalizes on technological advancements of research on electroencephalographic event-related potential and applies it to a novel PTSD population consisting of trauma-affected refugees. Methods: A total of 25 trauma-affected refugees with PTSD and 20 healthy refugee controls matched on age, gender, and country of origin completed the study. In two distinct auditory paradigms sensory gating, indexed as P50 suppression, and sensorimotor gating, indexed as prepulse inhibition (PPI), startle reactivity, and habituation of the eye-blink startle response were examined. Within the P50 paradigm, N100 and P200 amplitudes were also assessed. In addition, correlations between psychophysiological and clinical measures were investigated. Results: PTSD patients demonstrated significantly elevated stimuli responses across the two paradigms, reflected in both increased amplitude of the eye-blink startle response, and increased N100 and P200 amplitudes relative to healthy refugee controls. We found a trend toward reduced habituation in the patients, while the groups did not differ in PPI and P50 suppression. Among correlations, we found that eye-blink startle responses were associated with higher overall illness severity and lower levels of functioning. Conclusions: Fundamental gating mechanisms appeared intact, while the pattern of deficits in trauma-affected refugees with PTSD point toward a different form of sensory overload, an overall neural hypersensitivity and disrupted the ability to down-regulate stimuli responses. This study represents an initial step toward elucidating sensory processing deficits in a PTSD subgroup. [ABSTRACT FROM AUTHOR]

The complexity change in brain activity in schizophrenia is an interesting topic clinically. Schizophrenia patients exhibit abnormal task-related modulation of complexity, following entropy of electroencephalogram (EEG) analysis. However, complexity modulation in schizophrenia patients during the sensory gating (SG) task, remains unknown. In this study, the classical auditory paired-stimulus paradigm was introduced to investigate SG, and EEG data were recorded from 55 normal controls and 61 schizophrenia patients. Fuzzy entropy (FuzzyEn) was used to explore the complexity of brain activity under the conditions of baseline (BL) and the auditory paired-stimulus paradigm (S1 and S2). Generally, schizophrenia patients showed significantly higher FuzzyEn values in the frontal and occipital regions of interest (ROIs). Relative to the BL condition, the normalized values of FuzzyEn of normal controls were decreased greatly in condition S1 and showed less variance in condition S2. Schizophrenia patients showed a smaller decrease in the normalized values in condition S1. Moreover, schizophrenia patients showed significant diminution in the suppression ratios of FuzzyEn, attributed to the higher FuzzyEn values in condition S1. These results suggested that entropy modulation during the process of sensory information and SG was obvious in normal controls and significantly deficient in schizophrenia patients. Additionally, the FuzzyEn values measured in the frontal ROI were positively correlated with positive scores of Positive and Negative Syndrome Scale (PANSS), indicating that frontal entropy was a potential indicator in evaluating the clinical symptoms. However, negative associations were found between the FuzzyEn values of occipital ROIs and general and total scores of PANSS, likely reflecting the compensation effect in visual processing. Thus, our findings provided a deeper understanding of the deficits in sensory information processing and SG, which contribute to cognitive deficits and symptoms in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Movement execution in healthy individuals increases the somatosensory temporal discrimination threshold. These changes are a result of mechanisms of sensory gating at the subcortical level. Although the somatosensory temporal discrimination threshold is abnormally increased in patients with focal dystonias, the effect of movement execution on somatosensory temporal discrimination in dystonic patients is unknown.Objectives: The objective of this study was to determine whether somatosensory temporal discrimination threshold modulation induced by voluntary movement is normal in different forms of focal dystonia.Methods: We enrolled 71 dystonic patients (24 with blepharospasm, 31 with cervical dystonia, and 16 with focal hand dystonia) and 39 age-matched healthy participants. Paired stimuli for the somatosensory temporal discrimination threshold were triggered by movement execution at movement onset and at various time intervals thereafter. We analyzed the kinematic features of the motor task to ascertain whether tactile input induces changes in movement parameters.Results: Movement execution led to greater and longer lasting increases in somatosensory temporal discrimination threshold values, both upon movement onset and at various time intervals thereafter, in patients with cervical dystonia and focal hand dystonia than in those with blepharospasm or the healthy participants. Somatosensory temporal discrimination testing did not induce any changes in the mean velocity of index finger movements in either patients or healthy participants.Conclusions: Somatosensory temporal discrimination threshold changes induced by movement execution are abnormal in focal dystonias. This abnormality is related to the type of dystonia. Abnormal gating of sensory information is likely involved in movement-induced triggering or worsening of different forms focal dystonia. © 2018 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a Japanese version of the Sensory Gating Inventory (SGI; Hetrick, Erickson, & Smith, 2012) and to examine its reliability and validity. SGI measures abnormalities in the quality of sensory input, heightened awareness of background noises, and poor selective attention at the phenomenological level. The questionnaire was completed by 515 university and graduate students. The questionnaire package included 3 scales; 35 items from the Japanese version of SGI, 27 items from the Japanese version of the Highly Sensitive Person Scale (HSPS; Funahashi, 2011), and 25 items from the Japanese version of the Cognitive Failures Questionnaire (CFQ; Yamada, 1991). Confirmatory factor analysis showed that the Japanese SGI had an acceptable level of internal consistency. Cronbach's alpha was calculated to examine reliability and showed high values. Correlation analyses showed that the Japanese SGI and Japanese HSPS or CFQ were moderately positively correlated. This study suggests that the Japanese SGI is reliable and valid. It can be used to screen for abnormal sensory gating before physiological or behavioral inspection. [ABSTRACT FROM AUTHOR]

BackgroundAbnormal P50 response has been hypothesized to reflect the sensory gating deficit in schizophrenia. Despite the extensive literature concerning the sensory filtering or gating deficit in schizophrenia, no evidence has been provided to test the relationship of the P50 phenomenon with patients' experiences of perceptual anomalies.MethodsSixteen drug-free DSM-IV diagnosed schizophrenic patients who reported moderate to severe perceptual anomalies in the auditory or visual modality were examined as compared to 16 schizophrenic patients who did not report perceptual anomalies, and 16 normal subjects. Both control groups were age- and gender-matched with the study group.ResultsPatients reporting perceptual anomalies exhibited P50 patterns that did not differ from normal subjects. In contrast, patients who did not report perceptual anomalies showed the abnormal P50 ratios previously found to be associated with schizophrenia.ConclusionsThese paradoxical findings do not support the hypothetical relationship between the P50 and behavioral measures of sensory gating, suggesting that additional studies are needed to further explore the clinical correlates of the P50.

Brain electrophysiological responses can provide information about age-related decline in sensory-cognitive functions with high temporal accuracy. Studies have revealed impairments in early sensory gating and pre-attentive change detection mechanisms in older adults, but no magnetoencephalographic (MEG) studies have been undertaken into both non-attentive and attentive somatosensory functions and their relationship to ageing. Magnetoencephalography was utilized to record cortical somatosensory brain responses in young (20–28 yrs), middle-aged (46–56 yrs), and older adults (64–78 yrs) under active and passive somatosensory oddball conditions. A repeated standard stimulus was occasionally replaced by a deviant stimulus (p =.1), which was an electrical pulse on a different finger. We examined the amplitudes of M50 and M100 responses reflecting sensory gating, and later components reflecting change detection and attention shifting (M190 and M250 for the passive condition, and M200 and M350 for the active condition, respectively). Spatiotemporal cluster-based permutation tests revealed that older adults had significantly larger M100 component amplitudes than young adults for task-irrelevant stimuli in both passive and active condition. Older adults also showed a reduced M250 component and an altered M350 in response to deviant stimuli. The responses of middle-aged adults did not differ from those of younger adults, but this study should be repeated with a larger sample size. By demonstrating changes in both somatosensory gating and attentional shifting mechanisms, our findings extend previous research on the effects of ageing on pre-attentive and attentive brain functions. [Display omitted] • Somatosensory gating and change detection responses in ageing were studied in MEG. • Both active and passive stimulation conditions indicated ageing-related changes in MEG. • Older adults presented diminished sensory gating for task-irrelevant stimuli. • Older adults demonstrated altered attention shifting mechanisms. [ABSTRACT FROM AUTHOR]

• Acoustic trauma alters the functional connectivity of amygdala-thalamic circuitry. • Amygdala stimulation produces predominantly inhibition in the auditory thalamus. • Acoustic trauma did not significantly increase behavioural signs of anxiety. Acoustic trauma (AT) induced hearing loss elicits plasticity throughout the central auditory pathway, including at the level of the medial geniculate nucleus (MGN). Hearing loss also results in altered neuronal responses in the amygdala, which is involved in sensory gating at the level of the MGN. However, whether these altered responses in the amygdala affect sensory gating at the level of the MGN requires further evaluation. The current study aimed to investigate the effects of AT-induced hearing loss on the functional connectivity between the amygdala and the MGN. Male Sprague–Dawley rats were exposed to either sham (n = 5; no sound) or AT (n = 6; 16 kHz, 1 h, 124 dB SPL) under full anaesthesia. Auditory brainstem response (ABR) recordings were made to determine hearing thresholds. Two weeks post-exposure, extracellular recordings were used to assess the effect of electrical stimulation of the amygdala on tone-evoked (sham n = 22; AT n = 30) and spontaneous (sham n = 21; AT n = 29) activity of single neurons in the MGN. AT caused a large temporary and small permanent ABR threshold shift. Electrical stimulation of the amygdala induced differential effects (excitatory, inhibitory, or no effect) on both tone-evoked and spontaneous activity. In tone-evoked activity, electrical stimulation at 300 µA, maximum current, caused a significantly larger reduction in firing rate in AT animals compared to sham, due to an increase in the magnitude of inhibitory effects. In spontaneous activity, there was also a significantly larger magnitude of inhibitory effects following AT. The findings confirm that activation of the amygdala results in changes in MGN neuronal activity, and suggest the functional connectivity between the amygdala and the MGN is significantly altered following AT and subsequent hearing loss. [ABSTRACT FROM AUTHOR]