A Method for Simultaneous Evaluation of Muscular and Neural Prepulse Inhibition

Abstract

Prepulse inhibition (PPI) test has been widely used to evaluate sensorimotor gating. In humans, deficits in this mechanism are measured through the orbicularis muscle response using electromyography (EMG). Although this mechanism can be modulated by several brain structures and is impaired in some pathologies as schizophrenia and bipolar disorder, neural PPI evaluation is rarely performed in humans. Since eye blinks are a consequence of PPI stimulation, they strongly contaminate the electroencephalogram (EEG) signal. This paper describes a method to reduce muscular artifacts and enable neural PPI assessment through EEG in parallel to muscular PPI evaluation using EMG. Both types of signal were simultaneously recorded in 22 healthy subjects. PPI was evaluated by the acoustical startle response with EMG and by the P2-N1 event-related potential (ERP) using EEG in Fz, Cz, and Pz electrodes. In order to remove EEG artifacts, Independent Component Analysis (ICA) was performed using two methods. Firstly, visual inspection discarded components containing artifact characteristics as ocular and tonic muscle artifacts. The second method used visual inspection as gold standard to validate parameters in an automated component selection using the SASICA algorithm. As an outcome, EEG artifacts were effectively removed and equivalent neural PPI evaluation performance was obtained using both methods, with subjects exhibiting consistent neural as well as muscular PPI. This novel method improves PPI test, enabling neural gating mechanisms assessment within the latency of 100–200 ms, which is not evaluated by other sensory gating tests as P50 and mismatch negativity.

Early Schizophrenia and Bipolar Disorder Patients Display Reduced Neural Prepulse Inhibition

“…In addition, we observed reduction in neural %PPI for both BP and SZ patients. These findings suggest that the evaluation of neural PPI may detect gating impairments in a broader manner than the classical muscular PPI paradigm [ 52 ].…”

“…The frontal electrodes were the most contaminated by eye-blink artifacts, and the cleaning process may have attenuated the signal in these regions [ 72 ]. Sixth, there are several distinct protocols of PPI test, including different intensities, duration, and source of stimuli; herein, we opted to use a set up similar to those used in many studies with schizophrenia and/or bipolar patients [ 22 , 32 , 36 , 95 ] and those used in our previous study [ 52 ]. Seventh, we did match cases and controls for potential confounding variables (gender, age group, and educational level), but did not control for potential confounding of smoking status.…”

“…Artifactual components were automatically identified by the SASICA algorithm [ 72 ], with its parameters validated on the control group only. Our previous article, which validated our method to obtain neural PPI on the same control group used in this study, describes this procedure in detail [ 52 ], comparing it to other methods used in previous studies [ 76 , 77 , 78 ].…”

“…In those studies, patients with SZ show larger effect sizes than patients with BP in P50 [ 43 , 44 , 45 ], MMN [ 46 , 47 ], and P300 amplitude and latency [ 43 , 48 , 49 , 50 , 51 ], when compared to healthy controls. Neural PPI evaluates the neural gating phenomenon in the time window of 100–200 ms, whose latency is not explored by any other sensory gating paradigms [ 52 ]. However, neural PPI measurements have rarely been performed due to neural signal contamination resulting from strong muscular contractions elicited by the PPI-test stimuli.…”

“…However, neural PPI measurements have rarely been performed due to neural signal contamination resulting from strong muscular contractions elicited by the PPI-test stimuli. Fortunately, recent improvements on signal processing now support signal contamination reduction, allowing neural PPI assessment using electroencephalogram (EEG) alongside with classic eye-blink (muscular) [ 52 ]. The neural PPI is a more direct measure than the eye-blink muscular PPI and its psychopathological levels have been associated to eye-blink PPI impairment in SZ [ 53 , 54 , 55 , 56 ], but not in BP [ 34 , 57 ].…”