Inhibitory gating of an evoked response to repeated auditory stimuli in schizophrenic and normal subjects. Human recordings, computer simulation, and an animal model.
ABSTRACT Altered sensory response is a prominent feature of schizophrenia. Inhibitory gatting mechanisms, shown by diminished P50 evoked responses to repeated auditory stimuli, seem to be deficient in schizophrenic persons. These inhibitory mechanisms usually are studied by averaging the electroencephalographic responses to many presentations of pairs of stimuli. Although averaging increases signal-to-noise ratio, it may obscure trial-to-trial differences. We compared differences between schizophrenic and normal persons in single trials and averages of P50 response.
Recordings from 10 schizophrenic patients and 10 normal subjects were analyzed using conventional averaging and single-trial measurements. A computer simulation of both methods examined their ability to extract evoked responses from background activity. Related single-neuron activity in the hippocampus in an animal model also was studied, because neuronal action potentials can be reliably identified in single trials.
Averaged evoked potentials showed significant suppression of the P50 response to the second stimulus of the pair in normal patients, but not in schizophrenic patients. Single-trial analysis did not detect a response above background activity. Computer simulations gave similar results, suggesting that failure to detect suppression in single trials comes from inadequate differentiation of signal from noise. Recordings in animals confirmed almost complete suppression of the response of hippocampal pyramidal neurons to the second stimulus.
The normal inhibition of response to repeated auditory stimuli seems to be compromised in schizophrenia. This loss of inhibitory gating could reflect a physiological deficit of hippocampal interneurons that is consonant with other evidence for interneuron pathologic defects in schizophrenia.
SourceAvailable from: ejmanager.com[Show abstract] [Hide abstract]
ABSTRACT: ZET: Dikkat eksikliği hiperaktivite bozukluğu tanılı çocuk ve ergenlerde P50 duyusal kapılama ve metilfenidat tedavisinin P50 duyusal kapılama üzerine etkisi Amaç: P50 ölçümünün duyusal kapılama mekanizmasını yansıttığı ve insanlarda aşırı bilgi yüklenmesini önlediği düşünülmektedir. Dikkat eksikliği hiperaktivite bozukluğu (DEHB) hastalarında P50 işitsel olayla ilişkili yanıtın baskı-lanmasında yetersizlik olabilir. Bu araştırmanın amaçları P50 işitsel olayla ilişkili yanıtın baskılanmasını ve DEHB tanılı çocuk ve ergenlerde metilfenidat tedavisinin P50 paramet-releri üzerine olan etkilerinin ortaya konmasıdır. Yöntem: Araştırmaya DSM-IV tanı ölçütlerine göre DEHB (bileşik tip) tanısı konmuş, 9-14 yaşları arasında ilaç tedavisi verilmeyen 22 çocuk ve ergenle, 9-12 yaşları arasında zihinsel ve bedensel olarak sağlıklı 18 çocuk alınmıştır. Öncelikle ilaç tedavisi verilmeyen DEHB ve kontrol grubunda P50 değerleri ölçüldü. Bu ölçüm sonrası DEHB grubuna 10 mg metilfenidat verildi ve 1 saat sonra DEHB grubunda P50 ölçümü tekrarlan-dı. Kontrol grubunda P50 uygulaması tekrarlanmadı. Bulgular: DEHB ve sağlıklı kontrol grubu arasında P50 test latansı, test amplitütü ve P50 oranları açısından belirgin düzeyde anlamlı fark saptanmıştır. DEHB grubunda metil-fenidat öncesi ve metilfenidat verildikten sonra yapılan ölçümlerde koşullanma latansı, test latansı, test amplitütü ve P50 oranları açısından belirgin düzeyde anlamlı fark bulunmuştur. Sonuç: Bu araştırmanın sonuçları DEHB ile P50 arasında bir ilişki olduğuna ve metilfenidat uygulanmasının P50 baskılanma düzeyini artırdığına işaret etmektedir. Bu araş-tırma DEHB olan çocuk ve ergenlerde duyusal kapılamayı değerlendiren ilk çalışma olduğundan bir ön çalışma olarak görülmeli dir. Bu nedenle daha geniş örneklem sayılı araş-tırmalara gereksinim olduğu düşünülmektedir. Anahtar sözcükler: Dikkat eksikliği hiperaktivite bozuklu-ğu, çocuklar, P50, duyusal kapılama Kli nik Psi ko far ma ko lo ji Bül te ni 2011;21:42-48 ABS TRACT: P50 sensory gating in children and adolescents with ADHD and effects of methylphenidate administration on P50 sensory gating Objective: The P50 is thought to reflect a sensory gating mechanism and prevent information overload in humans. Failure to inhibit the P50 auditory event evoked response can occur in attention deficit hyperactivity disorder (ADHD) patients. The aims of the present study were to examine the inhibition of the P50 auditory event evoked potential and the effects of methyphenidate administration on P50 parameters in children and adolescents diagnosed with ADHD. Methods: Twenty-two drug-free subjects, aged 9-14, who were diagnosed with ADHD (the combined type) according to the DSM-IV criteria, and 18 mentally and physically healthy subjects, aged 9-12, were included in the study. First, P50 parameters were measured in drug-free ADHD subjects and healthy controls. Following this measurement, 10 mg of methylphenidate was administered to the ADHD group. The P50 measurement was repeated 1 hour following methylphenidate administration in the ADHD subjects. The healthy control group was not re-examined. Results: A significant difference was found in P50 test latency, test amplitude, and P50 ratio values between the ADHD group and healthy controls. Significant differences were also found in conditioning latency, test latency, test amplitude, and P50 ratio values between before and after methyphenidate administration in the ADHD group. Conclusions: The results of the present study point out an association between P50 and ADHD and they also show that methyphenidate administration increases the P50 suppression level. Since, this is the first study evaluating sensory gating in children and adolescents with ADHD, it should be considered as a preliminary study. Further studies with large study samples are warranted.Bulletin of Clinical Psychopharmacology 03/2011; DOI:10.5350/KPB-BCP201121107 · 0.37 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Synaptic plasticity alters the strength of information flow between presynaptic and postsynaptic neurons and thus modifies the likelihood that action potentials in a presynaptic neuron will lead to an action potential in a postsynaptic neuron. As such, synaptic plasticity and pathological changes in synaptic plasticity impact the synaptic computation which controls the information flow through the neural microcircuits responsible for the complex information processing necessary to drive adaptive behaviors. As current theories of neuropsychiatric disease suggest that distinct dysfunctions in neural circuit performance may critically underlie the unique symptoms of these diseases, pathological alterations in synaptic plasticity mechanisms may be fundamental to the disease process. Here we consider mechanisms of both short-term and long-term plasticity of synaptic transmission and their possible roles in information processing by neural microcircuits in both health and disease. As paradigms of neuropsychiatric diseases with strongly implicated risk genes, we discuss the findings in schizophrenia and autism and consider the alterations in synaptic plasticity and network function observed in both human studies and genetic mouse models of these diseases. Together these studies have begun to point toward a likely dominant role of short-term synaptic plasticity alterations in schizophrenia while dysfunction in autism spectrum disorders (ASDs) may be due to a combination of both short-term and long-term synaptic plasticity alterations.Frontiers in Synaptic Neuroscience 11/2014; 6:28. DOI:10.3389/fnsyn.2014.00028
[Show abstract] [Hide abstract]
ABSTRACT: Background: Individuals with an "Attenuated Psychosis Syndrome" (APS) have a 20–40% chance of developing a psychotic disorder within two years; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether P50 gating deficits could help to discriminate individuals with APS and also those who are particularly likely to make a transition to psychosis. Method: 36 cases meeting PACE (Personal Assessment and Crisis Evaluation) criteria for the APS, all free of anti-psychotics, and 60 controls performed an auditory conditioning–testing experiment while their electroenceph-alogram was recorded. The P50 ratio and its C–T difference were compared between groups. Subjects received follow-up for up to 2 years to determine their clinical outcome. Results: The P50 ratio was significantly higher and C–T difference lower in the APS group compared to controls. Of the individuals with APS who completed the follow-up (n = 36), nine (25%) developed psychosis. P50 ratio and the C–T difference did not significantly differ between those individuals who developed psychosis and those who did not within the APS group. Conclusion: P50 deficits appear to be associated with the pre-clinical phase of psychosis. However, due to the limitations of the study and its sample size, replication in an independent cohort is necessary, to clarify the role of P50 deficits in illness progression and whether this inexpensive and non-invasive EEG marker could be of clinical value in the prediction of psychosis outcomes amongst populations at risk.Schizophrenia Research 12/2014; 161(2-3). DOI:10.1016/j.schres.2014.12.021 · 4.43 Impact Factor