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1.
J Speech Lang Hear Res ; 67(3): 989-1001, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38386055

RESUMO

PURPOSE: Sensory gating is a phenomenon where the cortical response to the second stimulus in a pair of identical stimuli is inhibited. It is most often assessed in a conditioning-testing paradigm. Both active and passive neuronal mechanisms have been implicated in sensory gating. The present study aimed to assess if sensory gating is caused by an active neural mechanism associated with stimulus redundancy. METHOD: The study was carried out on 20 young neurotypical adults. We assessed the gating phenomenon using identical and nonidentical stimuli pairs presented in an electrophysiological conditioning-testing paradigm. We hypothesized that the novel stimulus in the nonidentical stimulus pair would not exhibit the sensory gating effects (reduction in the amplitude of cortical potentials to the second stimuli in the pair), owing to stimulus novelty. RESULTS: Contrary to our expectations, the response analyses of the cortical auditory evoked potentials revealed that adults gated repetitive and novel stimuli similarly. CONCLUSIONS: The findings are discussed in relation to the significance of methodological factors in evaluating sensory gating. We believe that additional research using oddball presentation of novel stimuli along with appropriate analysis methods is necessary before drawing any conclusions on the mechanisms underlying sensory gating.


Assuntos
Potenciais Evocados Auditivos , Filtro Sensorial , Adulto , Humanos , Potenciais Evocados Auditivos/fisiologia , Filtro Sensorial/fisiologia , Estimulação Acústica/métodos , Eletroencefalografia
2.
Respir Physiol Neurobiol ; 321: 104215, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38211904

RESUMO

Individuals with generalized anxiety disorder (GAD) have been shown to have altered neural gating of respiratory sensations (NGRS) using respiratory-related evoked potentials (RREP); however, corresponding neural oscillatory activities remain unexplored. The present study aimed to investigate altered NGRS in individuals with GAD using both time and time-frequency analysis. Nineteen individuals with GAD and 28 healthy controls were recruited. Paired inspiratory occlusions were delivered to elicit cortical neural activations measured from electroencephalography. The GAD group showed smaller N1 amplitudes to the first stimulus (S1), lower evoked gamma and larger evoked beta oscillations compared to controls. Both groups showed larger N1, P3, beta power and theta power in response to S1 compared to S2, suggesting a neural gating phenomenon. These findings suggest that N1, gamma and beta frequency oscillations may be indicators for altered respiratory sensation in GAD populations and that the N1, P3, beta and theta oscillations can reflect the neural gating of respiratory sensations.


Assuntos
Eletroencefalografia , Potenciais Evocados , Humanos , Potenciais Evocados/fisiologia , Transtornos de Ansiedade , Sensação , Taxa Respiratória , Filtro Sensorial/fisiologia
3.
Neuropsychopharmacology ; 49(2): 433-442, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37715107

RESUMO

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.


Assuntos
Proteínas de Transporte de Cátions , Esquizofrenia , Humanos , Camundongos , Animais , Estudo de Associação Genômica Ampla/métodos , Predisposição Genética para Doença/genética , Espinhas Dendríticas/metabolismo , Córtex Pré-Frontal/metabolismo , Cognição , Filtro Sensorial , Morfogênese , Polimorfismo de Nucleotídeo Único/genética , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-38160852

RESUMO

BACKGROUND: Psychiatric 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. METHODS: The 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. RESULTS: Baseline 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. CONCLUSION: The 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.


Assuntos
Dopamina , Ketamina , Animais , Humanos , Camundongos , Estimulação Acústica/métodos , Percepção Auditiva , Colinérgicos , Dopamina/fisiologia , Potenciais Evocados Auditivos/fisiologia , Filtro Sensorial
5.
Transl Psychiatry ; 13(1): 321, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37852987

RESUMO

Many neurodevelopmental disorders, including autism spectrum disorder (ASD), are associated with changes in sensory processing and sensorimotor gating. The acoustic startle response and prepulse inhibition (PPI) of startle are widely used translational measures for assessing sensory processing and sensorimotor gating, respectively. The Cntnap2 knockout (KO) rat has proven to be a valid model for ASD, displaying core symptoms, including sensory processing perturbations. Here, we used a novel method to assess startle and PPI in Cntnap2 KO rats that allows for the identification of separate scaling components: startle scaling, which is a change in startle amplitude to a given sound, and sound scaling, which reflects a change in sound processing. Cntnap2 KO rats show increased startle due to both an increased overall response (startle scaling) and a left shift of the sound/response curve (sound scaling). In the presence of a prepulse, wildtype rats show a reduction of startle due to both startle scaling and sound scaling, whereas Cntnap2 KO rats show normal startle scaling, but disrupted sound scaling, resulting in the reported PPI deficit. These results validate that startle and sound scaling by a prepulse are indeed two independent processes, with only the latter being impaired in Cntnap2 KO rats. As startle scaling is likely related to motor output and sound scaling to sound processing, this novel approach reveals additional information on the possible cause of PPI disruptions in preclinical models.


Assuntos
Transtorno do Espectro Autista , Reflexo de Sobressalto , Animais , Ratos , Estimulação Acústica/métodos , Transtorno do Espectro Autista/genética , Inibição Pré-Pulso , Reflexo de Sobressalto/fisiologia , Filtro Sensorial
6.
Dyslexia ; 29(4): 426-440, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37779260

RESUMO

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.


Assuntos
Dislexia , Humanos , Criança , Dislexia/complicações , Potenciais Evocados Auditivos/fisiologia , Leitura , Cognição , Filtro Sensorial
7.
J Psychopharmacol ; 37(11): 1116-1131, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37837354

RESUMO

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.


Assuntos
Cannabis , Zumbido , Camundongos , Masculino , Animais , Zumbido/tratamento farmacológico , Nicotina/farmacologia , Estimulação Acústica , Camundongos Endogâmicos C57BL , Filtro Sensorial
8.
Neuropsychologia ; 190: 108702, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37838067

RESUMO

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.


Assuntos
Potenciais Somatossensoriais Evocados , Magnetoencefalografia , Pessoa de Meia-Idade , Adulto Jovem , Humanos , Idoso , Potenciais Somatossensoriais Evocados/fisiologia , Encéfalo/fisiologia , Envelhecimento/fisiologia , Filtro Sensorial/fisiologia , Córtex Somatossensorial/fisiologia
9.
Arch Womens Ment Health ; 26(6): 793-801, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37673838

RESUMO

A large number of studies have reported that sensory gating disorders represented by P50 inhibition may be involved in the pathophysiological process of schizophrenia. However, few studies have explored the relationship between sensory gating disorders and cognitive dysfunction in patients with schizophrenia. This study aimed to explore sex differences in the relationship between cognitive and P50 deficits in patients with chronic schizophrenia, which has not been reported. A total of 183 chronic schizophrenia patients (128 males and 55 females) and 166 healthy controls (76 males and 90 females) participated in this study. The MATRICS Consensus Cognitive Battery (MCCB) was measured for cognitive function and P50 components for the sensory gating in all participants. The Positive and Negative Syndrome Scales (PANSS) was used to assess the psychopathological symptoms in patients. Female patients performed significantly better than male patients in several cognitive domains of MCCB (all p < 0.01). There were no significant differences in P50 components between male and female patients (all p > 0.05). Further analysis showed that in female patients, latency of S2 was negatively correlated with reasoning and problem-solving domain of MCCB (p < 0.05), and P50 ratio was negatively correlated with social cognition domain of MCCB (p < 0.05). In male patients, there was no any correlation between P50 and cognitive domains of MCCB. Our results suggest that there is a sex difference in the association between P50 deficiency and cognitive impairment in Chinese Han patients with schizophrenia.


Assuntos
Esquizofrenia , Caracteres Sexuais , Humanos , Masculino , Feminino , Esquizofrenia/diagnóstico , Cognição , Povo Asiático , Filtro Sensorial/fisiologia , Testes Neuropsicológicos
10.
Am J Audiol ; 32(4): 889-897, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37725711

RESUMO

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.


Assuntos
Percepção da Fala , Humanos , Percepção da Fala/fisiologia , Fala , Potenciais Evocados Auditivos/fisiologia , Ruído , Filtro Sensorial , Estimulação Acústica/métodos
11.
Methods Mol Biol ; 2687: 57-64, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37464162

RESUMO

Prepulse inhibition of the startle response enables measuring animal behavior and helps us understand core aspects of neuropsychiatric diseases. Prepulse inhibition is considered a translational indicator of sensorimotor gating deficits present in schizophrenia patients and is crucial in the characterization of animal models of schizophrenia-like behaviors. Hallucinogenic drugs acting through 5-HT2A receptors, such as psilocybin, lysergic acid diethylamide (LSD), and dimethoxyiodoamphetamine (DOI), produce symptoms in healthy subjects comparable to those seen in schizophrenia and can be used in rodent models for mimicking some of these behaviors. Here we describe a protocol for the evaluation of prepulse inhibition of the startle response in CD1-Swiss male mice after a single dose of the hallucinogenic drug DOI.


Assuntos
Inibição Pré-Pulso , Esquizofrenia , Camundongos , Masculino , Animais , Reflexo de Sobressalto/fisiologia , Filtro Sensorial
12.
Psychol Med ; 53(6): 2540-2552, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37310299

RESUMO

BACKGROUND: Diminished sensory gating (SG) is a robust finding in psychotic disorders, but studies of early psychosis (EP) are rare. It is unknown whether SG deficit leads to poor neurocognitive, social, and/or real-world functioning. This study aimed to explore the longitudinal relationships between SG and these variables. METHODS: Seventy-nine EP patients and 88 healthy controls (HCs) were recruited at baseline. Thirty-three and 20 EP patients completed 12-month and 24-month follow-up, respectively. SG was measured using the auditory dual-click (S1 & S2) paradigm and quantified as P50 ratio (S2/S1) and difference (S1-S2). Cognition, real-life functioning, and symptoms were assessed using the MATRICS Consensus Cognitive Battery, Global Functioning: Social (GFS) and Role (GFR), Multnomah Community Ability Scale (MCAS), Awareness of Social Inference Test (TASIT), and the Positive and Negative Syndrome Scale (PANSS). Analysis of variance (ANOVA), chi-square, mixed model, correlation and regression analyses were used for group comparisons and relationships among variables controlling for potential confounding variables. RESULTS: In EP patients, P50 ratio (p < 0.05) and difference (p < 0.001) at 24-month showed significant differences compared with that at baseline. At baseline, P50 indices (ratio, S1-S2 difference, S1) were independently associated with GFR in HCs (all p < 0.05); in EP patients, S2 amplitude was independently associated with GFS (p = 0.037). At 12-month and 24-month, P50 indices (ratio, S1, S2) was independently associated with MCAS (all p < 0.05). S1-S2 difference was a trending predictor of future function (GFS or MCAS). CONCLUSIONS: SG showed progressive reduction in EP patients. P50 indices were related to real-life functioning.


Assuntos
Transtornos Psicóticos , Cognição Social , Humanos , Seguimentos , Análise de Variância , Filtro Sensorial
13.
Psychopharmacology (Berl) ; 240(6): 1359-1372, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37129616

RESUMO

RATIONALE: The prepulse inhibition (PPI) of the startle reflex is the best-established index of sensorimotor gating. We documented that the neurosteroid allopregnanolone (AP) is necessary to reduce PPI in response to D1 dopamine receptor agonists. Since Sprague-Dawley (SD) rats are poorly sensitive to the PPI-disrupting effects of these drugs, we hypothesized that AP might increase this susceptibility. OBJECTIVES: We tested whether AP is sufficient to increase the vulnerability of SD rats to PPI deficits in response to the D1 receptor full agonist SKF82958. METHODS: SD rats were tested for PPI after treatment with SKF82958 (0.05-0.3 mg/kg, SC) in combination with either intraperitoneal (1-10 mg/kg) or intracerebral (0.5 µg/µl/side) AP administration into the medial prefrontal cortex (mPFC) or nucleus accumbens shell. To rule out potential confounds, we measured whether SKF82958 affected the endogenous mPFC levels of AP. RESULTS: SD rats exhibited marked PPI deficits in response to the combination of systemic and intra-mPFC AP with SKF82958 but not with the D2 receptor agonist quinpirole (0.3-0.6 mg/kg, SC). SKF82958 did not elevate mPFC levels of AP but enhanced the content of its precursor progesterone. The PPI deficits caused by SKF82958 in combination with AP were opposed by the AP antagonist isoallopregnanolone (10 mg/kg, IP) and the glutamate NMDA receptor positive modulator CIQ (5 mg/kg, IP). CONCLUSION: These results suggest that AP enables the detrimental effects of D1 receptor activation on sensorimotor gating. AP antagonism or glutamatergic modulation counters these effects and may have therapeutic potential for neuropsychiatric disorders characterized by gating deficits.


Assuntos
Pregnanolona , Receptores de Dopamina D1 , Ratos , Animais , Masculino , Ratos Sprague-Dawley , Pregnanolona/farmacologia , Benzazepinas/farmacologia , Reflexo de Sobressalto , Filtro Sensorial , Estimulação Acústica/métodos
14.
Behav Brain Res ; 449: 114487, 2023 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-37169130

RESUMO

Sensorimotor gating is a measure of pre-attentional information processing and can be measured by prepulse inhibition (PPI) of the startle reflex. Sleep deprivation has been shown to disrupt PPI in animals and humans, and has been proposed as an early phase 2 model to probe antipsychotic efficacy in heathy humans. To further investigate the reliability and efficacy of sleep deprivation to produce PPI deficits we tested the effects of total sleep deprivation (TSD) on PPI in healthy controls in a highly controlled sleep laboratory environment. Participants spent 4 days and nights in a controlled laboratory environment with their sleep monitored with polysomnography. Participants were randomly assigned to either normal sleep on all 4 nights (N = 17) or 36 h of TSD on the 3rd or 4th night (N = 40). Participants were assessed for sleepiness using the Karolinska Sleepiness Scale (KSS) and underwent a daily PPI task (interstimlulus intervals 30-2000 ms) in the evening. Both within-subject effects (TSD vs. normal sleep in TSD group alone) and between-subject effects (TSD vs. no TSD group) of TSD on PPI were assessed. TSD increased subjective sleepiness measured with the KSS, but did not significantly alter overall startle, habituation or PPI. Sleep measures including duration, rapid eye movement and slow wave sleep duration were also not associated with PPI performance. The current results show that human sensorimotor gating may not be reliably sensitive to sleep deprivation. Further research is required for TSD to be considered a dependable model of PPI disruption for drug discovery in humans.


Assuntos
Privação do Sono , Sonolência , Animais , Humanos , Reprodutibilidade dos Testes , Atenção/fisiologia , Sono , Filtro Sensorial/fisiologia , Reflexo de Sobressalto/fisiologia
15.
PLoS One ; 18(5): e0277446, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37205689

RESUMO

Protein Tyrosine Phosphatase receptor type D (PTPRD) is a member of the protein tyrosine phosphatase family that mediates cell adhesion and synaptic specification. Genetic studies have linked Ptprd to several neuropsychiatric phenotypes, including Restless Leg Syndrome (RLS), opioid abuse disorder, and antipsychotic-induced weight gain. Genome-wide association studies (GWAS) of either pediatric obsessive-compulsive traits, or Obsessive-Compulsive Disorder (OCD), have identified loci near PTPRD as genome-wide significant, or strongly suggestive for this trait. We assessed Ptprd wild-type (WT), heterozygous (HT), and knockout (KO) mice for behavioral dimensions that are altered in OCD, including anxiety and exploration (open field test, dig test), perseverative behavior (splash-induced grooming, spatial d), sensorimotor gating (prepulse inhibition), and home cage goal-directed behavior (nest building). No effect of genotype was observed in any measure of the open field test, dig test, or splash test. However, Ptprd KO mice of both sexes showed impairments in nest building behavior. Finally, female, but not male, Ptprd KO mice showed deficits in prepulse inhibition, an operational measure of sensorimotor gating that is reduced in female, but not male, OCD patients. Our results indicate that constitutive lack of Ptprd may contribute to the development of certain domains that are altered OCD, including goal-directed behavior, and reduced sensorimotor gating specifically in females.


Assuntos
Estudo de Associação Genômica Ampla , Transtorno Obsessivo-Compulsivo , Masculino , Feminino , Animais , Camundongos , Objetivos , Transtorno Obsessivo-Compulsivo/genética , Genótipo , Inibição Pré-Pulso , Camundongos Knockout , Filtro Sensorial/genética , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética
16.
Behav Brain Res ; 450: 114498, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37201892

RESUMO

The medial geniculate body (MGB) of the thalamus is an obligatory relay for auditory processing. A breakdown of adaptive filtering and sensory gating at this level may lead to multiple auditory dysfunctions, while high-frequency stimulation (HFS) of the MGB might mitigate aberrant sensory gating. To further investigate the sensory gating functions of the MGB, this study (i) recorded electrophysiological evoked potentials in response to continuous auditory stimulation, and (ii) assessed the effect of MGB HFS on these responses in noise-exposed and control animals. Pure-tone sequences were presented to assess differential sensory gating functions associated with stimulus pitch, grouping (pairing), and temporal regularity. Evoked potentials were recorded from the MGB and acquired before and after HFS (100 Hz). All animals (unexposed and noise-exposed, pre- and post-HFS) showed gating for pitch and grouping. Unexposed animals also showed gating for temporal regularity not found in noise-exposed animals. Moreover, only noise-exposed animals showed restoration comparable to the typical EP amplitude suppression following MGB HFS. The current findings confirm adaptive thalamic sensory gating based on different sound characteristics and provide evidence that temporal regularity affects MGB auditory signaling.


Assuntos
Córtex Auditivo , Tálamo , Ratos , Animais , Tálamo/fisiologia , Corpos Geniculados/fisiologia , Estimulação Acústica , Sensação , Filtro Sensorial , Córtex Auditivo/fisiologia
17.
Res Child Adolesc Psychopathol ; 51(7): 1005-1019, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37014483

RESUMO

This review aimed to explore the current understanding of sensory gating in neurodevelopmental disorders as a possible transdiagnostic mechanism. We applied methods according to the Joanna Briggs Institute Manual for Evidence Synthesis, following the population, concept, and context scoping review eligibility criteria. Using a comprehensive search strategy in five relevant research databases (Medline, EMBASE, CINAHL, PsychInfo, and Scopus), we searched for relevant peer-reviewed, primary research articles and unpublished data. Two independent reviewers screened the titles and abstracts, full-texts, and completed data extraction. We identified a total of 81 relevant articles and used descriptive analyses to summarize the characteristics and outcomes of all identified studies. Literature regarding sensory gating was most common in autistic populations with relatively fewer studies examining attention-deficit/hyperactivity disorder, tic disorders, and childhood-onset fluency disorder (COFD). The methods to assess sensory gating varied widely both within and between groups and included measures such as habituation, prepulse inhibition, affect-modulated inhibition, medication and other intervention trials. Most consistently, when participants complete questionnaires about their sensory experiences, those who have neurodevelopmental disorders report differences in their sensory gating. Affect-modulated inhibition appears to be discrepant between samples with and without neurodevelopmental disorder diagnoses. Habituation was the most commonly reported phenomenon and many differences in habituation have been found in autistic individuals and individuals with tic disorders whereas concerns with inhibition seemed more common in COFD. Overall, the evidence is inconsistent within and between disorders suggesting there is still much to learn about sensory gating in neurodevelopmental disorders.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno Autístico , Transtornos do Neurodesenvolvimento , Transtornos de Tique , Humanos , Criança , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtornos de Tique/tratamento farmacológico , Filtro Sensorial
18.
Schizophr Res ; 255: 148-154, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36989672

RESUMO

INTRODUCTION: Noradrenergic imbalance in the brain of schizophrenia patients may underlie both symptomatology and deficits in basic information processing. The current study investigated whether augmentation with the noradrenergic α2-agonist clonidine might alleviate these symptoms. METHODS: In a double-blind placebo-controlled randomized clinical trial, 32 chronic schizophrenia patients were randomly assigned to six-weeks augmentation with either 50 µg clonidine or placebo to their current medication. Effects on symptom severity and both sensory- and sensorimotor gating were assessed at baseline, 3- and 6-weeks. Results were compared with 21 age- and sex-matched healthy controls (HC) who received no treatment. RESULTS: Only patients treated with clonidine showed significantly reduced PANSS negative, general and total scores at follow-up compared to baseline. On average, also patients treated with placebo showed minor (non-significant) reductions in these scores, likely indicating a placebo effect. Sensorimotor gating of patients was significantly lower at baseline compared to controls. It increased in patients treated with clonidine over the treatment period, whereas it decreased in both the HC and patients treated with placebo. However, neither treatment nor group effects were found in sensory gating. Clonidine treatment was very well tolerated. CONCLUSION: Only patients treated with clonidine showed a significant decrease on two out of the three PANSS subscales, while additionally retained their levels of sensorimotor gating. Given that there are only a few reports on effective treatment for negative symptoms in particular, our current results support augmentation of antipsychotics with clonidine as a promising, low-cost and safe treatment strategy for schizophrenia.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/induzido quimicamente , Clonidina/uso terapêutico , Clonidina/farmacologia , Antipsicóticos/efeitos adversos , Filtro Sensorial , Quimioterapia Combinada , Resultado do Tratamento , Método Duplo-Cego , Escalas de Graduação Psiquiátrica
19.
J Exp Psychol Hum Percept Perform ; 49(4): 496-511, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36972084

RESUMO

Prepulse inhibition (PPI) is an automatic and pre-attentive sensorimotor gating process. Several studies have shown that advanced cognitive functions can modulate PPI. This study aimed to further elucidate the modulatory effect of attentional resource allocation on PPI. We examined the differences in PPI between high and low attentional loads. First, we verified that the adapted feature versus combination visual search paradigm could produce high and low perceptual load differences according to the task demands. Second, we measured the participants' task-unrelated PPI during the visual search task and found that the PPI in the high-load condition was significantly lower than that in the low-load condition. To further elucidate the role of attentional resources, we tested task-related PPI using a dual-task paradigm in which participants were instructed to complete a visual task with an auditory discrimination task. We found a result similar to that of the task-unrelated experiment. The participants in the high-load condition had less PPI than those in the low-load condition. Finally, we ruled out the possibility that the working memory load explains the modulation of PPI. In line with the theory of PPI modulation, these results suggest that allocating limited attentional resources to the prepulse modulates PPI. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Atenção , Inibição Pré-Pulso , Humanos , Inibição Pré-Pulso/fisiologia , Estimulação Acústica/métodos , Atenção/fisiologia , Filtro Sensorial/fisiologia , Cognição
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