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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 µV and greater than 0.5 µV. 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 α-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 α-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.
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