Sensory gating refers to the pre-attentional habituation of responses to repeated exposure to the same sensory stimulus. The inhibition of responsiveness to repetitive stimulation provides humans with the ability to negotiate a sensory-laden environment by blocking out irrelevant, meaningless, or redundant stimuli. P50 is an electroencephalogram (EEG) event-related potential waveform used to assess sensory gating.
There is a large body of evidence to suggest that a significant proportion of patients with schizophrenia have sensory gating impairments.1
These studies have formed the foundation for several hypothetical constructs of the pathophysiology of the symptoms of schizophrenia.2,3
Some theorists suggest that the positive and perhaps the negative symptoms of schizophrenia are a result of sensory overload and/or an impairment in the response to sensory input within the central nervous system, a theoretical concept that originated with Venables.4
Sensory gating abnormalities have also been hypothesized to be associated with various cognitive impairments.5–9
Efforts to delineate the neuroanatomy and neurochemistry of the P50 measure of sensory gating have yielded inconsistent findings, across both species and measurement techniques. Integrating work from human and animal studies, Freedman and colleagues8
suggested that the hippocampus was the primary region implicated in sensory gating, and that multiple neurotransmitters were involved, including the cholinergic, dopaminergic, GABAergic, glutamatergic, noradrenergic, and serotonergic systems. Other recent attempts to localize P50 have relied on magnetoencephalography (MEG) and intracranial recording. MEG-based source analyses have localized P50 generators in several different regions, including Heschl's gyrus10
and the superior temporal gyrus.11
Another set of putative sources for scalp-measured P50 has emerged from intracranial recordings, including prefrontal cortex,12
Gating in the hippocampus, however, was temporally distinct from P50, occurring at a longer latency,12
and may not be reflected in P50. Given the disparate findings across localization studies in humans, it is not possible to delineate clearly the neural circuitry responsible for P50 gating.
Pharmacological studies, however, have demonstrated the importance of the cholinergic system in regulating the diminished response to repeated stimuli, through stimulation of the α-7 nicotinic receptor.8,9,15–19
In patients with schizophrenia, nicotine can transiently reverse the P50 sensory gating deficit.8,20,21
This finding suggests that pharmacological treatments could be developed that modulate P50 with the potential of symptomatic improvement for patients with schizophrenia.
More recently, a marker of the gene for the α-7 nicotinic receptor has been linked to schizophrenia and P50 abnormalities.16
There is also evidence to suggest that polymorphisms in the promotor region of the gene for the α-7 nicotinic receptor may be related to abnormal sensory gating.22
Further supporting a genetic basis of a sensory gating abnormality in schizophrenia has been evidence that family members of people with schizophrenia also have deficits in P50 sensory gating inhibition at higher rates than baseline populations.20,23–26
Additional evidence for a genetic underpinning is provided by patients with schizophrenia spectrum disorders, such as schizotypal personality disorder, who also demonstrate this deficit in gating.27
The hypothesized association of P50 abnormalities with various domains of schizophrenia pathology, the ability to pharmacologically modify the P50 abnormality, and the genetic underpinnings of the P50 abnormality have stimulated the development of novel drugs designed to reverse P50 abnormalities in schizophrenia. If P50 is to be used as a target to guide drug development, then questions arise as to what other illness components are related to P50 abnormalities and what are the clinical implications of enhanced P50 performance. The purpose of this review is to ascertain the clinical significance of P50-related gating abnormalities in patients with schizophrenia. This review will look at studies that have examined the relationship of P50 to neuropsychological measures, symptoms, treatment, and other electrophysiological markers.