Age and sex effects on paired-pulse suppression and prepulse inhibition of auditory evoked potentials.

Responses to a sensory stimulus are inhibited by a preceding stimulus; if the two stimuli are identical, paired-pulse suppression (PPS) occurs; if the preceding stimulus is too weak to reliably elicit the target response, prepulse inhibition (PPI) occurs. PPS and PPI represent excitability changes in neural circuits induced by the first stimulus, but involve different mechanisms and are impaired in different diseases, e.g., impaired PPS in schizophrenia and Alzheimer's disease and impaired PPI in schizophrenia and movement disorders. Therefore, these measures provide information on several inhibitory mechanisms that may have roles in clinical conditions. In the present study, PPS and PPI of the auditory change-related cortical response were examined to establish normative data on healthy subjects (35 females and 32 males, aged 19-70 years). We also investigated the effects of age and sex on PPS and PPI to clarify whether these variables need to be considered as biases. The test response was elicited by an abrupt increase in sound pressure in a continuous sound and was recorded by electroencephalography. In the PPS experiment, the two change stimuli to elicit the cortical response were a 15-dB increase from the background of 65 dB separated by 600 ms. In the PPI experiment, the prepulse and test stimuli were 2- and 10-dB increases, respectively, with an interval of 50 ms. The results obtained showed that sex exerted similar effects on the two measures, with females having stronger test responses and weaker inhibition. On the other hand, age exerted different effects: aging correlated with stronger test responses and weaker inhibition in the PPS experiment, but had no effects in the PPI experiment. The present results suggest age and sex biases in addition to normative data on PPS and PPI of auditory change-related potentials. PPS and PPI, as well as other similar paradigms, such as P50 gating, may have different and common mechanisms. Collectively, they may provide insights into the pathophysiologies of diseases with impaired inhibitory function.

The Auditory P50 Gating in Mild Cognitive Impairment: A Case-Control Study.

Objective: Auditory P50 gating changed might be a neurophysiological biomarker of the diagnosis of Mild Cognitive Impairment (MCI). We aimed to determine the impact of MCI in auditory P50 gating. Methods: All recruited participants completed structured questionnaires and finished auditory P50 gating measure. Results: A total of 20 MCI patients and 17 controls had been recruited. MCI patients had a significant higher reduction of P50 gating at Fz site, when compared to controls (1.21 ± .68 vs .66 ± .37, P = .00). Zero point five was the best cut off point to distinguish MCI and control of auditory P50 gating S2/S1 at Fz site. The P50 average amplitude at Pz site in MCI patients was significantly higher than controls (2.62 ± 1.20 vs 1.70 ± .74, P = .01). Conclusion: MCI patients might have impaired the ability of inhibiting the repeated stimulus.

Prepulse inhibition of the acoustic startle reflex and P50 gating in aging and alzheimer's disease.

Inhibition plays a crucial role in many functional domains, such as cognition, emotion, and actions. Studies on cognitive aging demonstrate changes in inhibitory mechanisms are age- and pathology-related. Prepulse inhibition (PPI) is the suppression of an acoustic startle reflex (ASR) to an intense stimulus when a weak prepulse stimulus precedes the startle stimulus. A reduction of PPI is thought to reflect dysfunction of sensorimotor gating which normally suppresses excessive behavioral responses to disruptive stimuli. Both human and rodent studies show age-dependent alterations of PPI of the ASR that are further compromised in Alzheimer's disease (AD). The auditory P50 gating, an index of repetition suppression, also is characterized as a putative electrophysiological biomarker of prodromal AD. This review provides the latest evidence of age- and AD-associated impairment of sensorimotor gating based upon both human and rodent studies, as well as the AD-related disruption of P50 gating in humans. It begins with a concise review of neural networks underlying PPI regulation. Then, evidence of age- and AD-related dysfunction of both PPI and P50 gating is discussed. The attentional/ emotional aspects of sensorimotor gating and the neurotransmitter mechanisms underpinning PPI and P50 gating are also reviewed. The review ends with conclusions and research directions.

Startle Modification and P50 Gating in Schizophrenia Patients and Controls: Russian Population.

Prepulse modification of the acoustic startle response (ASR) and P50 gating are potential neurophysiological endophenotypes of schizophrenia and may be used in the construction of valid clinical biomarkers. Such approach requires a large amount of data obtained in the representative samples from different gender, socio-typological and ethnic groups, replicating studies using the similar protocols and meta-analyses. This is a replication study of ASR and the first study of P50 suppression in Russian patients with schizophrenia (n = 28) and healthy controls (n = 25). ASR and P50 were estimated according to standard protocols. Patients exhibited increased baseline ASR latency (d = 0.35, p = .026) and reduced prepulse inhibition (PPI) at 60 ms interval (d = 0.39, p = .003) and 120 ms interval (d = 0.37, p = .005) relative to controls. In the P50 test patients displayed greater S2 response amplitude (d = 0.24, p = .036) and deficit of P50 suppression (d = 0.43, p = .001). No correlations of PPI and P50 suppression were found in both groups. Only in controls prepulse ASR facilitation (at 2500 ms interval) positively correlated with P50 suppression (r = -.514, p = .013). In patients PPI displayed significant correlations with Difficulty in abstract thinking (N5: r = -.49, p = .005) and Hallucination (P3: r = .40, p = .036) PANSS scales. Logistic regression showed that the combination of PPI and P50 suppression could serve as a diagnostic predictor. Obtained results demonstrated that both PPI and P50 could be regarded as potential schizophrenia biomarkers in Russian population.

Clarifying the functional process represented by P50 suppression.

P50 suppression refers to the amplitude-reduction of the P50 event related potential to the second (S2) relative to the first (S1) of identical auditory stimuli presented 500ms apart. Theory suggests that refractory periods (RPs) and/or inhibitory inputs (II) underlie P50 suppression. The present study manipulated interval between stimulus pairs (IPI: 2, 8s) and direction of participants' attention (Attention, Non-Attention) in order to determine which theory best explains P50 suppression. The rationale is that: 1/ RP and II predict opposite effects of manipulating the functionality of the mechanism responsible for S2P50 suppression (e.g. reducing function would increase S2P50 according to the II and decrease S2P50 according to the RP hypothesis); 2/ IPI2 (relative to IPI8) will reduce functionality of the mechanism responsible for S2P50 suppression, as it results in less recovery of (and a greater challenge to) that mechanism - RP would thus predict reduced S2P50, whereas II would predict enhanced S2P50 amplitude; and 3/ where the mechanism responsible for S2P50 suppression is challenged (i.e. at IPI2, due to insufficient recovery), Attention (relative to Non-Attention) will enhance functionality of this mechanism - RP would thus predict increased S2P50, whereas II would predict reduced S2P50 amplitude. In the Non-Attention paradigm, reducing IPI from 8 to 2s tended to increase S2P50 amplitude (and consequently impaired P50 suppression), and in the 2s IPI paradigm, directing attention towards the stimuli reduced S2P50 amplitude (and improved P50 suppression), with both effects supporting the II hypothesis only.

Smoking, MATRICS consensus cognitive battery and P50 sensory gating in a Han Chinese population.

BACKGROUND: The effects of smoking on cognitive performance have long been studied, with mixed results. P50 sensory gating has been used as endophenotype for studying nicotinic systems genetics, and P50 gating deficits have been reported to be a sensitive biomarker for cognitive impairment in schizophrenia. This study examined the inter-relationship between P50 suppression, cognitive function, and smoking in a healthy Han Chinese population, which has not been reported before. METHODS: We recruited 82 healthy male subjects, including 48 smokers and 34 non-smokers who were matched for age and education. The authors measured P50 sensory gating and administered the Chinese-language version of the MATRICS consensus cognitive battery (MCCB) and Stroop tests. RESULTS: The results showed that the smokers scored lower than nonsmokers on the MCCB brief visuospatial memory test (BVMT) index and the STROOP test. Furthermore, the MCCB total score was negatively associated with number of cigarettes smoked per day in the smoker group. However, P50 sensory gating was not associated with either smoking status or any cognitive performance. CONCLUSIONS: Our results show that smoking is associated with cognitive impairment, but not with P50 sensory gating.