Study of P50 sensory gating deficit in schizophrenic patients with violent and aggressive behaviors / 四川精神卫生

ObjectiveTo assess the specificity of P50 auditory-evoked potential in schizophrenic patients with violent and aggressive behaviors， so as to provide objective biological markers for predicting violent behaviors of schizophrenic patients. MethodsA total of135 schizophrenic patients who met the diagnostic criteria of the International Classification of Diseases， tenth edition （ICD-10） were divided into aggressive group （n=70） and non-aggressive group （n=65） according to the assessment results of the Modified Overt Aggression Scale （MOAS）， meantime， another 60 healthy individuals matched for age and gender were set as healthy group. Then the P50 auditory-evoked potentials of all selected individuals were measured using EP/EMG system （MEB-9200， Nihon Kohden， Japan）. ResultsAmp S2 of the aggressive group was significantly higher than those of the non-aggressive group and healthy control group， with statistical differences ［（9.86±6.04）μV vs. （7.06±3.88）μV， P=0.004； （9.86±6.04）μV vs. （7.82±3.87）μV， P=0.031］. The proportion of S2/S1 ratio ≥0.5 was 72.88%， 43.86% and 30.00% in aggressive group， non-aggressive group and healthy group， which was the highest in aggressive group， with statistical differences （P<0.01）. The amplitude difference of P50 （S1-S2） of the aggressive group was lower than those of the non-aggressive group and the healthy control group， the differences were of statistical significance ［（4.35±9.39）μV vs.（9.89±8.48）μV， P=0.001； （4.35±9.39）μV vs.（13.42±9.81）μV， P<0.01］. ConclusionThe violent and aggressive behaviors in schizophrenic patients may be related to the sensory gating deficit.

A Computational Modeling Reveals That Strength of Inhibitory Input, E/I Balance, and Distance of Excitatory Input Modulate Thalamocortical Bursting Properties

The thalamus is a brain structure known to modulate sensory information before relaying to the cortex. The unique ability of a thalamocortical (TC) neuron to switch between the high frequency burst firing and single spike tonic firing has been implicated to have a key role in sensory modulation including pain. Of the two firing modes, burst firing, especially maintaining certain burst firing properties, was suggested to be critical in controlling nociceptive behaviors. Therefore, understanding the factors that influence burst firing properties would offer important insight into understanding sensory modulation. Using computational modeling, we investigated how the balance of excitatory and inhibitory inputs into a TC neuron influence TC bursting properties. We found that intensity of inhibitory inputs and the timing of excitatory input delivery control the dynamics of bursting properties. Then, to reflect a more realistic model, excitatory inputs delivered at different dendritic locations—proximal, intermediate, or distal—of a TC neuron were also investigated. Interestingly, excitatory input delivered into a distal dendrite, despite the furthest distance, had the strongest influence in shaping burst firing properties, suggesting that not all inputs equally contribute to modulating TC bursting properties. Overall, the results provide computational insights in understanding the detailed mechanism of the factors influencing temporal pattern of thalamic bursts.

Effects of Ketamine on Basal Gamma Band Oscillation and Sensory Gating in Prefrontal Cortex of Awake Rats / 神经科学通报·英文版

Gamma band oscillation (GBO) and sensory gating (SG) are associated with many cognitive functions. Ketamine induces deficits of GBO and SG in the prefrontal cortex (PFC). However, the time-courses of the effects of different doses of ketamine on GBO power and SG are poorly understood. Studies have indicated that GBO power and SG have a common substrate for their generation and abnormalities. In this study, we found that (1) ketamine administration increased GBO power in the PFC in rats differently in the low- and high-dose groups; (2) auditory SG was significantly lower than baseline in the 30 mg/kg and 60 mg/kg groups, but not in the 15 mg/kg and 120 mg/kg groups; and (3) changes in SG and basal GBO power were significantly correlated in awake rats. These results indicate a relationship between mechanisms underlying auditory SG and GBO power.

Effect of Oxygen Inhalation on Auditory Sensory Gating P50 / 中国康复理论与实践

@#Objective To explore the effect of oxygen inhalation on auditory sensory gating P50 in healthy human brain. Methods 28 healthy male academician right-handed were included. They were divided into control group (n=12) and experiment group (n=16) according to the random numerical table, and blinded about groups. The subjects inhaled pure oxygen in the experiment group, and air in the control group through a mask for 60 min. The electroencephalograph was recorded while an auditory paired-click sensory gating test was conducted during 4 study periods: before inhalation (pre0), inhale for 20 min (Oxy20) and 50 min (Oxy50), and 30 min after inhalation (post30). The latency and amplitude (S1-S2) of auditory sensory gating P50 were calculated. Results The latencies of P50 from S1 were stable in each group (P>0.7), and the latency of Oxy50 was shorter in the experiment group than in the control group (P<0.05). The latencies from S2 were stable in each group (P>0.30), and there was no significant difference between groups in all the time points (P>0.05). The amplitudes of (S1-S2) of P50 were stable in the control group (P=0.70), and was higher on Oxy20 (P=0.04) and Oxy50 (P=0.02) than post30 in the experiment group. There was no difference between the groups in all the time points (P>0.05). Conclusion Oxygen inhalation may be helpful to shorten the active time to stimulate, and trend to enhancing the amplitude of P50.

Effect of Oxygen Inhalation on Auditory Sensory Gating P50 / 中国康复理论与实践

Objective To explore the effect of oxygen inhalation on auditory sensory gating P50 in healthy human brain. Methods 28 healthy male academician right-handed were included. They were divided into control group (n=12) and experiment group (n=16) according to the random numerical table, and blinded about groups. The subjects inhaled pure oxygen in the experiment group, and air in the control group through a mask for 60 min. The electroencephalograph was recorded while an auditory paired-click sensory gating test was conducted during 4 study periods:before inhalation (pre0), inhale for 20 min (Oxy20) and 50 min (Oxy50), and 30 min after inhalation (post30). The la-tency and amplitude (S1-S2) of auditory sensory gating P50 were calculated. Results The latencies of P50 from S1 were stable in each group (P>0.7), and the latency of Oxy50 was shorter in the experiment group than in the control group (P0.30), and there was no significant difference between groups in all the time points (P>0.05). The amplitudes of (S1-S2) of P50 were stable in the control group (P=0.70), and was higher on Oxy20 (P=0.04) and Oxy50 (P=0.02) than post30 in the experi-ment group. There was no difference between the groups in all the time points (P>0.05). Conclusion Oxygen inhalation may be helpful to shorten the active time to stimulate, and trend to enhancing the amplitude of P50.

The functional magnetic resonance imaging (fMRI) study of auditory sensory gating in the siblings of schizophrenic / 中国神经精神疾病杂志

Objective To investigate auditory sensory gating potential in the siblings of schizophrenic, to discover the neuroimaging features of sensory gating associated with schizophrenia as intermediate phenotypes. Methods Twelve siblings of schizophrenia patients in the first episodic, and 12 healthy controls matched in gender, age, education under?went MRI scan when performing a auditory sensory gating fMRI task (repeated clicks and single click auditory stimuli). The measure of sensory gating was the contrast of repeated clicks minus single click. The analysis of result was imple?mented in SPM2. Results Compared with healthy controls, schizophrenia patients showed significant overactivation in the right inter cingulate gyrus (x=4,y=8,z=32) and left anterior cingulate gyrus (x=-8,y=4,z=28) during the fMRI senso?ry gating task. Conclusion Sensory gating is overactivated in the cingulate gyrus in siblings of schizophrenic. This pat?tern may be a potential endophenotype of schizophrenia.

Effect of Oxygen Inhalation on Auditory Sensory Gating P50 / 中国康复理论与实践

@#Objective To explore the effect of oxygen inhalation on auditory sensory gating P50 in healthy human brain. Methods 28 healthy male academician right-handed were included. They were divided into control group (n=12) and experiment group (n=16) according to the random numerical table, and blinded about groups. The subjects inhaled pure oxygen in the experiment group, and air in the control group through a mask for 60 min. The electroencephalograph was recorded while an auditory paired-click sensory gating test was conducted during 4 study periods: before inhalation (pre0), inhale for 20 min (Oxy20) and 50 min (Oxy50), and 30 min after inhalation (post30). The latency and amplitude (S1-S2) of auditory sensory gating P50 were calculated. Results The latencies of P50 from S1 were stable in each group (P>0.7), and the latency of Oxy50 was shorter in the experiment group than in the control group (P<0.05). The latencies from S2 were stable in each group (P>0.30), and there was no significant difference between groups in all the time points (P>0.05). The amplitudes of (S1-S2) of P50 were stable in the control group (P=0.70), and was higher on Oxy20 (P=0.04) and Oxy50 (P=0.02) than post30 in the experiment group. There was no difference between the groups in all the time points (P>0.05). Conclusion Oxygen inhalation may be helpful to shorten the active time to stimulate, and trend to enhancing the amplitude of P50.

Effect of Oxygen Inhalation on Auditory Sensory Gating P50 / 中国康复理论与实践

@#Objective To explore the effect of oxygen inhalation on auditory sensory gating P50 in healthy human brain. Methods 28 healthy male academician right-handed were included. They were divided into control group (n=12) and experiment group (n=16) according to the random numerical table, and blinded about groups. The subjects inhaled pure oxygen in the experiment group, and air in the control group through a mask for 60 min. The electroencephalograph was recorded while an auditory paired-click sensory gating test was conducted during 4 study periods: before inhalation (pre0), inhale for 20 min (Oxy20) and 50 min (Oxy50), and 30 min after inhalation (post30). The latency and amplitude (S1-S2) of auditory sensory gating P50 were calculated. Results The latencies of P50 from S1 were stable in each group (P>0.7), and the latency of Oxy50 was shorter in the experiment group than in the control group (P<0.05). The latencies from S2 were stable in each group (P>0.30), and there was no significant difference between groups in all the time points (P>0.05). The amplitudes of (S1-S2) of P50 were stable in the control group (P=0.70), and was higher on Oxy20 (P=0.04) and Oxy50 (P=0.02) than post30 in the experiment group. There was no difference between the groups in all the time points (P>0.05). Conclusion Oxygen inhalation may be helpful to shorten the active time to stimulate, and trend to enhancing the amplitude of P50.

Study on the P50 Auditory Evoked Potential in Mood Disorder Subjects / 신경정신의학

OBJECTIVES: Diminished suppression of the P50 response, a consistent finding in schizophrenia, has also been reported in patients with bipolar disorder. It is a promising endophenotype for schizophrenia, but its relationship to genetic liability in mood disorder is controversial. The present study investigated event-related brain potential (ERP) indices of auditory processing and sensory gating in mood disorder and subgroups of patients with bipolar disorder with or without a history of psychosis using the P50 dual-click procedure. METHODS: The P50 auditory evoked potential response to paired stimuli was measured in 77 subjects with mood disorder (58 with bipolar disorder and 19 with major depressive disorder) and 28 healthy controls. P50 parameters were compared between groups. RESULTS: P50 suppression in patients with mood disorder did not differ from that in the healthy subjects. Except for S1 latency, there were no significant differences in P50 parameters between the diagnosis groups. In patients with bipolar disorder, a history of psychosis made no difference to P50 parameters. CONCLUSION: P50 was not significantly impaired in patients with mood disorder. There has been much debate on the meaning of P50, and more studies including longitudinal within-subjects studies are warranted to clarify the meaning and mechanisms of P50.

Follow-up study on auditory sensory gating P50 in schizophrenia patients with homicide / 中国神经精神疾病杂志

Objective To investigate the auditory sensory gating P50 in schizophrenia patients with homicide during three months of follow up. Methods Twenty-five patients with schizophrenia patients with homicide and 27 healthy adults matched with age and education level were recruited in the present study. P50 was recorded in twenty-seven normal controls and twenty-five schizophrenia patients at the baseline. P50 was repeatedly recorded in eleven patients who completed the follow-up at three months following antipsychotics treatment. The psychotic symptoms of patients were assessed with Positive and Negative Syndrome Scale (PANSS) at the same time. Results ①In comparison with normal controls, schizophrenia patients with homicide showed increased S2-P50 amplitude (P<0.01), increased S2/S1 ratio (P<0.01), decreased S1-S2(P<0.05), and 100(1-S2/S1) (P<0.01) at the baseline and after three months treatment. The differences in P50 amplitude, latency, and P50 suppression index between the baseline and after three-month treatment in schizophrenia patients with homicide were not significant (P>0.05). ② Schizophrenia patients with homicide after three-month treatment showed decreased PANSS total scale, positive scale, general psychopathology scale, and six symptoms scales such as lack of response, thought disorder, activation, paranoid, depression, and aggression (P<0.05). ③ No significant correlations were found between the S2/S1 ratio, S2-S1, and 100(1-S2/S1) with disease duration, PANSS scores, and six symptoms scales at either baseline or after three-month treatment (P>0.05). Conclusions Schizophrenia with homicide has sensory gating deficits and P50 suppression index might be a stable trait maker for schizophrenia with homicide.

The effects of olanzapine,clozapine,risperidone and quetiapine treatment on P50 sensory gating in first-ep-isode schizophrenics / 中华行为医学与脑科学杂志

Objective To compare the effects of atypical antipsyehoties treatment on PS0 sensory gating in first-episode schizophrenics. Methods The P50 auditory evoked potential was recorded by using conditioning-testing stimulus paradigm and stimulus train paradigm in 36 normal controls and 53 first-episode schizophrenics be-fore and after treatment,and compare the difference of P50 sensory gating after treatment. Results Before treat-ment, compared with control group, the atypical groups both had statistic difference of T-P50 amplitude ((1.01±0.88)μV, (0.68±0.64)μV, (0.58±0.47)μV), P50 suppression ((0.61±0.27), (0.54±0.22, (0. 59± 0.19)) in conditioning-testing stimulus paradigm and P50 amplitude,P50 suppression evoked by high frequency stimuli in stimulus train paradigm(P < 0.05), but no difference among the atypical groups (P > 0.05). After treat-ment,compared with control group, there was no statistic difference in olanzapine and elozapine groups of T-P50 amplitude and P50 suppression in conditioning-testing stimulus paradigm, but the difference in risperidone and que-tiapine groups still obviously(P<0.05). In stimulus train paradigm, there was no statistic difference of P50 ampli-tude, P50 suppression evoked by high frequency stimuli in every groups (P>0.05). Compared within atypical groups, the difference of P50 amplitude and P50 suppression were both obviously(P<0.05). Conclusion Each a-typical antipsychotic has different effect on P50 sensory gating;and the conditioning-testing stimulus paradigm and stimulus train paradigm P50 sensory gating may reflect different central neuron mechanism.

The effects of typical and atypical antipsychotics on P50 sensory gating in first-episode schizophrenics / 中国神经精神疾病杂志

Objective To compare the effects of typical and atypical antipsychotics treatment on P50 sensory ga-ting in first-episode schizophrenics.Methods Using conditioning-testing stimulus paradigm and stimulus train paradigm to record the P50 auditory evoked potential in 36 normal controls and in 61 first-episode schizophrenics before and after treat-ment.Patients were categorized into two groups:the typical antipsychotic treatment group(typical group)and the atypical antipsychotic treatment group(atypical group).Results Before treatment,both of the typical and atypical groups had low-er levels of S2-P50 amplitude,P50 suppression in conditioning-testing stimulus paradigm and P50 amplitude as well as P50 suppression evoked by high frequency stimuli in stimulus train paradigm in comparison with controls(P<0.05).After treatment,the typical antipsychotic treatment significantly improved the levels of P50 suppression in the stimulus train para-digm but not the levels of S2-P50 amplitude,P50 suppression in the conditioning-testing stimulus paradigm(P<0.05)whereas the atypical antipsychotic treatment improve the levels of P50 amplitude,P50 suppression in both stimulus train paradigm and the conditioning-testing stimulus paradigm(P<0.05). Conclusions The typical antipsychotic treatment can ameliorate the P50 suppression in stimulus train paradigm,but not in the conditioning-testing stimulus paradigm,whereas atypical antipsychotic treatment can ameliorate P50 suppression in both paradigms.

Filtrado sensorial y P50: implicaciones para la neurobiología de la esquizofrenia

Resumen: El estudio del filtrado sensorial mediante potenciales evocados ha marcado una línea de investigación en la esquizofrenia que plantea explicaciones alternativas a la presencia de la sintomatología, y que bien merecen atención y estudio. La P50 es un potencial evocado con respuesta de latencia media que se origina en el lóbulo temporal medio, en el hipocampo y cerca de éste. Mediante estudios con magnetoencefalografía, se ha propuesto que las células piramidales situadas en el giro temporal son la fuente más probable de la P50 en el registro electroencefalográfico, correspondiente al electrodo CZ situado en el vértex, de acuerdo con el sistema internacional 10-20. En este paradigma se presentan ensayos con dos estímulos auditivos con sonido de "clic": el primero es condicionante (E1) y el segundo, de prueba (E2), y pueden tener parámetros variables de duración, intensidad, intervalo interestímulo e intervalo interensayo. Cuando existe variación en los valores de estos parámetros, se obtiene como resultado una respuesta facilitada o suprimida al segundo estímulo. La P50 es una onda con amplitud no mayor a 50 -i.V ni menor a 0.5 -i.V. Para su análisis, se saca un promedio de entre 30 y 180 ensayos de cada estímulo y finalmente se analiza mediante la comparación del porcentaje de disminución de la amplitud de E1 y de E2, también con el resultado de la diferencia de E1 menos E2, o con el porcentaje de disminución en el área de la P50 de E2 comparada con la disminución de Et Los estudios que documentan la eficacia de los antipsicóticos para normalizar el defecto en el filtrado sensorial no brindan información concluyente. Algunos estudios han observado que los pacientes sin medicación antipsicótica no presentan supresión de la respuesta a E2, o la presentan muy disminuida. Otros estu dios han documentado la repuesta no suprimida de la P50 en un grupo de esquizofrénicos bajo tratamiento antipsicótico. En ellos se observó un aumento en las latencias y amplitudes del trazo casi idénticas que las presentadas por los controles sanos. Se ha descri to que la mejoría en el déficit sensorial que presentan los esquizofrénicos bajo tratamiento antipsicótico se debe al bloqueo de la transmisión dopaminérgica. Se ha observado que algunos de los familiares en primer grado de los pacientes con esquizofrenia muestran también alteraciones en la inhibición del segundo estímulo auditivo del paradigma P50. Asimismo, en familiares sanos no fumadores que presentaban el defecto de filtrado se ha reportado una normalización transitoria del déficit sensorial registrado después de dosificar nicotina me diante goma de mascar. De acuerdo con estos datos, se ha propuesto la importancia que tiene la nicotina para el filtrado sensorial. En el paradigma de la P50, el fenómeno de habituación se produce cuando E1 activa las interneuronas a través de los receptores nicotínicos, que provocan la liberación de GABA, con la cual las células piramidales del hipocampo no logran ser excitadas por E2 y por lo tanto no responden a éste. En la esquizofrenia, la falta de habituación puede explicarse por una disminución en el número de interneuronas inhibitorias que muestran una alta ex presión de receptores nicotínicos.

Abstract: In the search for etiologic and physiologic keys to increase the knowledge about schizophrenia, research focused in the assessment of sensory gating by the use of event-related potentials has been considered an alternative to explain the presence of cognitive and positive symptoms. The P50 is a middlelatency-evoked potential originated in the temporal lobe, in the hippocampus and close to this. Through magnetoencephalographic studies, it has been hypothesized that piramidal cells located in the temporal gyrus are the most suitable source of the P50 wave present in electroencephalographic recordings. Therefore, the main wave for the obtention of the P50 is located in the vertex, which corresponds to the CZ electrode, in agreement with the 10-20 International System. The P50 paradigm is evoked by two auditory stimuli with the sound of a click, where the first stimulus is labelled conditioning (S1) and the second one, testing (S2). Both of them may have variable values for duration, intensity, inter-stimulus interval and inter-testing interval. Any variation on these parameter values leads to a suppressed or a facilitated response of the second stimulus. The amplitude established for the P50 paradigm is smaller than 50 [íV and greater than 0.5 -iV. Once the recording is acquired, the analysis of the P50 wave must be done with an average of 30 to 180 tests of S1 and S2. Results from the average can be analyzed by: a) a comparison of the amplitude's diminution percentage of S1 and S2, b) the difference between the substraction of the S1 value minus the S2 value, or c) the mean reduction of the P50 area of S1 compared with the mean reduction of the P50 area of S2. Different pharmacological assays had shown evidence of changes in sensory gating performance by means of the mechanism of action of some antipsychotics. Although some studies had shown a normalizing effect of antipsychotics over the sensory gating deficit in schizophrenic patients, the results are not conclusive. Some studies have reported that schizophrenic patients under antipsychotic treatment suppress the S2, while patients without antipsychotic treatment showed a lack of suppression of the S2. Nevertheless, other studies had reported a minor suppression of the second stimulus in groups of schizophrenic patients under antipsychotic treatment. Moreover, other studies had observed increased latencies and almost identical amplitudes of the outline between schizophrenic patients and normal healthy controls. The dopamine hypothesis has been one of the most important physiopathologic explanations for schizophrenia and the dopaminergic transmission blockade has also been implicated in the improvement of sensory gating in schizophrenic patients under antipsychotic treatment. Furthermore, a familiar pattern of sensory gating dysfunction has been found in healthy first-degree relatives of schizophrenic patients, whose response to the P50 paradigm has shown the lack of inhibition to the second auditory stimulus. This deficit is mainly observed in the parent having a greater familiar history for schizophrenia and also in half of the patient's healthy sibs. It is important to consider that although some relatives display an abnormal performance of the P50 wave, in general their cognitive performance is higher than the one showed by the schizophrenic patient. Likewise, some healthy non-smoker relatives, whose previous recordings displayed abnormal P50 waves, showed a transitory normalization of their sensory gating after nicotine administration by means of a nicotine chewing gum. It has been postulated that nicotine has a primary effect over the sensory gating performance. Hippocampal neurons receiving the originating stimuli from the medial septal nucleus are densely concentrated with nicotinic receptors. This inervation has been described as the main filter of repetitive auditory stimuli in the hippocampus. Following the hypothesis of the influence of nicotine over the sensory gating performance, it has been proposed that the habituation phenomenon occuring in the P50 paradigm takes place when interneurons are activated by nicotinic receptors after the first auditory stimuli. This activation causes a liberation of GABA, which avoids hippocampal piramidal cells excitation by S2, and therefore they do not respond to this stimulus. In schizophrenic patients, the lack of habituation can be explained by histochemical evidencies which suggest a smaller number of inhibitory interneurons with a higher expression of OC-7 nicotinic receptors. Based on these data, the actual background of the P50 paradigm brings out the possibility of including it as an important biological marker for the early detection of schizophrenia between high-risk relatives of schizophrenic patients. Further research is required to fully understand the potential advantages offered by the P50 sensory gating study. It is important to develop pharmacological studies focused on the role of specific antipsychotics over cognitive functions in schizophrenic patients. Also, future research should be addressed to the assessment of the influence of nicotinic receptors in attentional proceses and in the etiopathology of schizophrenia in order to explore O -7 nicotinic receptor selective agonists as candidates for the treatment of cognitive and perceptual disturbances in schizophrenia. The aim of this review is to give an introduction to the auditory sensory gating studies applied to schizophrenia research by means of event-related potentials.