Effects of P50 temporal variability on sensory gating in schizophrenia

Abstract

The conditioning-testing (S1-S2) P50 auditory evoked potential (EP) has been well-documented and accepted as an important tool for measuring sensory gating in schizophrenia research. However, the physiological mechanism of the phenomenon is not known. In this study a single-trial analysis was used to determine the influence of the latency variability of the responses in the formation of the averaged P50. Ten schizophrenic patients and 10 normal controls were tested in the dual-click EP paradigm. Using ensemble averaging analysis, we replicated the previous finding of a lower S1 P50 amplitude and higher S2/S1 ratio in schizophrenics compared with normal controls. The single-trial analysis revealed that patients had significantly higher trial-to-trial latency variability in S1 responses than normal subjects, while the S2 showed the same variability as in controls. Measured by the single-trial procedure, the arithmetic mean amplitudes of P50 responses to S1 and S2 were similar between normal and schizophrenic subjects. The same measure also eliminated the difference in averaged P50 amplitude between S1 and S2 for both groups. Temporal variability appears to be an important factor in the assessment of averaged EPs and thus contribute to the change of P50 amplitude observed in schizophrenia.

Pattern of P50 suppression deficit in patients with epilepsy and individuals with schizophrenia

“…Such increase was found in all groups of patients with epilepsy, regardless of seizure control. In agreement with the results reported here, several authors have found that the decrease in P50 suppression in patients with schizophrenia is due to a smaller amplitude of S1, although some increase in the amplitude of S2 has also been reported 11,[17][18][19][20] . One possible explanation is that there may be a direct effect on the inhibition of the response to the second stimulus in epilepsy, thus leading to greater amplitude of S2.…”

“…The sensory filter depends on complex brain circuits. In schizophrenia, the decrease in the S2/S1 ratio is usually due to a decrease in S1 amplitude 11,[17][18][19][20] , whereas in other disorders, such as Machado-Joseph disease 18 and traumatic brain injury 4 , S2 amplitude is increased, which may indicate the existence of different mechanisms affecting the sensory filter.…”

Micromolar Brain Levels of Kynurenic Acid are Associated with a Disruption of Auditory Sensory Gating in the Rat

“…Our hypothesis was based on evidence implicating glutamatergic and cholinergic receptors in sensory gating (Adler et al, 1986;Luntz-Leybman et al, 1992;Miller et al, 1992a;Bickford and Wear, 1995) and on data showing that cortical and CSF KYNA levels are elevated in schizophrenia (Erhardt et al, 2001;Schwarcz et al, 2001), a disorder characterized by marked auditory gating deficits (Adler et al, 1982;Boutros et al, 1991;Jin et al, 1997;Clementz et al, 1998a, b;Patterson et al, 2000). Since KYNA penetrates the bloodbrain barrier very poorly (Fukui et al, 1991), an indirect approach was implemented, involving blockade of the PBCD-sensitive transporter alone and in conjunction with the administration of KYNA's immediate bioprecursor KYN.…”

“…Altered responsiveness to auditory stimuli has also been observed in humans. Thus, several laboratories have reported that the amplitude of the conditioning response is significantly reduced in schizophrenic patients (Jin et al, 1997;Patterson et al, 2000;Blumenfeld and Clementz, 2001). Moreover, in normal controls, the amplitude of the conditioning response is more tightly correlated with other indices of sensory gating (e.g.…”

“…The diminished response to the second tone is thought to reflect the neural processes involved in gating sensory input and is typically quantified as the ratio of test to conditioning (T/C) response amplitude (Adler et al, 1999;Light and Braff, 1999). Numerous studies have demonstrated that persons with schizophrenia exhibit a blunted response to conditioning stimuli and a failure to show the characteristic reduction in ERP amplitude to the test stimulus (Adler et al, 1982;Boutros et al, 1991;Jin et al, 1997;Clementz et al, 1998a, b;Patterson et al, 2000). Notably, these deficits are strongly correlated with neuropsychological measures of attention (Erwin et al, 1998) and vigilance (Cullum et al, 1993).…”