پیش بینی حساسیت به حواس پرتی در اسکیزوفرنی با اختلال پردازش حسی اولیه

Abstract Patients with schizophrenia frequently report difficulties paying attention during important tasks, because they are distracted by noise in the environment. The neurobiological mechanism underlying this problem is, however, poorly understood. The goal of this study was to determine if early sensory processing deficits contribute to sensitivity to distracting noise in schizophrenia. To that end, we examined the effect of environmentally relevant distracting noise on performance of an attention task in 19 patients with schizophrenia and 22 age and gender-matched healthy comparison subjects. Using electroencephalography, P50 auditory gating ratios also were measured in the same subjects and were examined for their relationship to noise-induced changes in performance on the attention task. Positive symptoms also were evaluated in patients. Distracting noise caused a greater increase in reaction time in patients, relative to comparison subjects, on the attention task. Higher P50 auditory gating ratios also were observed in patients. P50 gating ratio significantly correlated with the magnitude of noise-induced increase in reaction time. Noise-induced increase in reaction time was associated with delusional thoughts in patients. P50 ratios were associated with delusional thoughts and hallucinations in patients. In conclusion, the observation of noise effects on attention in patients is consistent with subjective reports from patients. The observed relationship between noise effects on reaction time and P50 auditory gating supports the hypothesis that early inhibitory processing deficits may contribute to susceptibility to distraction in the illness

Introduction During early investigations of sensory perception in schizophrenia, McGhie and Chapman observed that patients often complained about being overwhelmed by sensory stimuli, as if they were “overflooded” with information to the point where it became impossible to focus on any specific stimulus (McGhie and Chapman, 1961). The investigators hypothesized that patients had a fundamental deficit in “the selective and inhibitory functions of attention,” such that “consciousness would be flooded with an undifferentiated mass of incoming sensory data.” These deficits may contribute to positive symptoms in patients, as they may “attach important meanings to insignificant events” and become sensitive to and suspicious of the environment (Weckowicz, 1958). Distractibility in patients has since been confirmed in numerous studies that have reported increased error rates as well as increased reaction times on various tasks in the presence of irrelevant stimuli compared to controls (Grillon et al., 1990, Lawson et al., 1967, McGhie et al., 1965a, McGhie et al., 1965b, Payne and Caird, 1967 and Steffy and Galbraith, 1975). The deficit may be especially pronounced using auditory tasks with auditory distractors (McGhie et al., 1965a and Lawson et al., 1967). Patients whose positive symptoms persist to a greater degree following treatment may be particularly susceptible to auditory distraction (Green and Walker, 1986 and Walker and Harvey, 1986). Deficits in the “inhibitory functions of attention” may arise due to several factors, including pathology of prefrontal-cortical processes involved in the voluntary control of attention (so called “top-down” effects) as well as disruptions in early sensory processes (i.e. “bottom-up” effects). Although the vast majority of research on the neurobiology of schizophrenia has focused on dysfunction in cognitive, “top-down” areas (such as the prefrontal cortex), a growing body of literature suggests that early sensory processing might also be disrupted in the illness (Javitt, 2009). Using electroencephalography (EEG), studies have consistently reported abnormalities in early (often 50 or 100 ms latency) event related potential responses (ERPs) to stimuli in patients with schizophrenia. The P50 is an early auditory evoked response to a stimulus that exhibits reduced amplitude when a second stimulus is presented 500 ms following the first. This reduction, usually studied in the auditory domain with repeated pairs of clicks, is referred to as P50 gating and may be a mechanism for automated, early inhibitory control and filtering of responses to repetitive stimuli (Roth and Kopell, 1969), preventing organisms from being overwhelmed by redundant sensory stimulation in the environment (Croft et al., 2001). The magnitude of inhibition is defined as the ratio of the evoked response amplitude to the first stimulus (S1) to the evoked response amplitude of the second stimulus (S2) (i.e. S1/S1), or P50 ratio. This inhibition is often reduced or eliminated in patients with schizophrenia, demonstrating a failure in sensory gating that may be related to stimulus “overflooding” (Patterson et al., 2008). Thus, inhibitory failure of S2 suppression may be a mechanism by which patients are more distracted by irrelevant environmental stimuli. Nonetheless, evidence that P50 gating is associated with related symptomatology (e.g. poor selective attention or perceptual abnormalities) is limited and findings are mixed. Two studies have found an association between poor sensory gating and attentional deficits (Cullum et al., 1993 and Erwin et al., 1998). In contrast, another study found no association between perceptual abnormalities (assessed by interview) and P50 ratio (Jin et al., 1998). Associations between P50 ratio and working memory as well as processing speed have also been reported (Potter et al., 2006). However, to our knowledge, no study has examined the relationship between distractibility (defined here as impaired selective attention) in schizophrenia and P50 gating. In the present study, we examined the effect of an environmentally relevant noise distraction on performance of an auditory attention task in schizophrenia patients and healthy comparison subjects. The distracting urban noise stimulus is a mixture of common sounds from the environment simulating what a person may experience in a real-life urban setting, including multiple conversations and noises recorded from a party, music, and conversations from the radio (Tregellas et al., 2009). To determine if early sensory processing contributes to the effects of distracting noise on attention, P50 auditory gating ratios were measured and examined for their relationship to noise-induced changes in performance on the attention task. We hypothesized that patients would show more pronounced performance deficits during noise, and that the magnitude of this deficit would be associated with impaired sensory gating. Additionally, given previous suggestions that distractibility may be related to positive symptoms, we hypothesize that both noise effects and P50 gating would be associated with BPRS measures of hallucinations and delusions in patients.

3. Results 3.1. Attention task Behavioral data are presented in Table 1. For errors of commission, a significant main effect of group was observed (F(1,39) = 20.8, p < 0.001), with patients making more errors than controls. No main effect of distraction (F(1,39) = 0.94, p = 0.34), or distraction (noise or silence) × diagnosis (patient or control) interaction (F(1,39) = 0.01, p = 0.92) was observed. Similarly, for errors of omission, a significant main effect of group was observed (F(1,39) = 11.2, p = 0.002), with patients making more errors than controls. No main effect of distraction (F(1,39) = 0.65, p = 0.42) or distraction × diagnosis interaction (F(1,39) = 0.06, p = 0.81) was observed. Table 1. Behavioral and EEG data. Controls S.D. Patients S.D. P50 conditioning amplitude (μV) 3.35 1.27 2.82 2.11 P50 test amplitude (μV) 0.89 0.71 1.45 1.41 P50 ratio (conditioning/test) 0.28 0.19 0.60 0.48 %Errors of commission in silence 5.30 7.95 21.0 16.5 %Errors of commission in noise 7.20 7.39 23.4 18.5 Change in %errors of commission (noise–silence) 1.89 11.9 2.34 16.0 %Errors of omission in silence 2.72 4.81 12.4 14.2 %Errors of omission in noise 2.16 6.20 11.4 11.6 Change in %errors of omission (noise–silence) − 0.56 2.96 − 1.00 8.34 RT in silence (ms) 413 72.0 391 110 RT during noise (ms) 411 82.3 435 84.6 Change in RT (noise–silence) (ms) − 1.91 47.1 43.7 79.5 Table options For reaction time, no main effect of group was observed (F(1,39) = 0.0, p = 0.99). However, a significant main effect of distraction (F(1,39) = 4.33, p = 0.044) as well as a significant distraction × diagnosis interaction (F(1,39) = 5.16, p = 0.029) were both observed. Post-hoc tests showed that the significant interaction was driven by significantly increased reaction times during noise (relative to silence) in patients (p = 0.005) but no effect of noise on reaction times in controls (p = 0.89) (Fig. 1). Comparison of the effect of noise on RT between schizophrenia patients and ... Fig. 1. Comparison of the effect of noise on RT between schizophrenia patients and healthy controls. Error bars represent the standard error of the mean. Figure options Across all subjects, no relationship was observed between noise-induced changes in %errors of commission and changes in reaction time (R = 0.10, F(1,39) = 0.41, p = 0.52) or noise-induced changes in %errors of omission and changes in reaction time (R = 0.048, F(1,39) = 0.091, p = 0.76). 3.2. P50 sensory gating P50 auditory sensory gating ratios were greater in patients, relative to comparison subjects (t = 2.62, df = 34, p = 0.02) (Table 1). Across all subjects, gating ratio was positively correlated with noise-induced changes in reaction time on the attention task (R = 0.45, F(1,34) = 8.87, p = 0.005; Fig. 2). Within the patient group alone, gating ratio was also positively correlated with noise-induced changes in reaction time (R = 0.48, F(1,15) = 4.51, p = 0.05). Within the control group alone, gating ratio was not correlated with noise-induced changes in reaction time (R = 0.10, F(1,17) = 0.18, p = 0.67). When gating ratio was used as a covariate, the difference in noise-induced reaction time between patients and controls was no longer significant (F (1,33) = 0.58, p = 0.45). Correlation between gating ratio and the effect of noise on RT during the task. ... Fig. 2. Correlation between gating ratio and the effect of noise on RT during the task. Statistics: Across all subjects, R = 0.45, F(1,34) = 8.87, p = 0.005; patient group alone, R = 0.48, F(1,15) = 4.51, p = 0.05. Figure options The relationships between P50 response to the first (conditioning, or S1) and second (test, or S2) stimuli and the effect of noise on reaction times were also examined. Across all subjects, S1 was not significantly associated with noise-induced changes in reaction time (R = 0.11, F(1,34) = 0.39, p = 0.53). In contrast, across all subjects, S2 was significantly associated with noise-induced changes in reaction time (R = 0.42, F(1,34) = 7.36, p = 0.010). Within the patient group alone, S2 was also significantly associated with the effect of noise on reaction time (R = 0.64, F(1,15) = 10.2, p = 0.006). Within the control group alone, S2 was not correlated with noise-induced change in reaction time (R = 0.27, F(1,17) = 1.32, p = 0.27). 3.3. Clinical correlates In patients, noise-induced increase in reaction time was significantly associated with unusual thought content (i.e. delusional thoughts) on the BPRS (Spearman's rho = 0.57, p = 0.018). P50 ratios showed a nearly significant positive correlation with unusual thought content on the BPRS (Spearman's rho = 0.49, p = 0.056). No significant correlation was observed between noise-induced increase in reaction time and the Hallucinations subscore on the BPRS (Spearman's rho = 0.23, p = 0.38). A significant correlation was observed between P50 ratio and the Hallucinations subscore (Spearman's rho = 0.55, p = 0.03).