محرومیت از خواب واکنش پذیری مردمک به محرک های عاطفی در بزرگسالان جوان و سالم را تغییر می دهد

Abstract The aim of this pilot study was to quantify the impact of sleep deprivation on psychophysiological reactivity to emotional stimuli. Following an adaptation night of sleep in the lab, healthy young adults were randomly assigned to either one night of total sleep deprivation or to a normal sleep control condition. The next afternoon, responses to positive, negative, and neutral picture stimuli were examined with pupillography, an indicator of cognitive and affective information processing. Only the sleep-deprived group displayed significantly larger pupil diameter while viewing negative pictures compared to positive or neutral pictures. The sleep-deprived group also showed anticipatory pupillary reactivity during blocks of negative pictures. These data suggest that sleep deprivation is associated with increased reactions to negative emotional information. Such responses may have important implications for psychiatric disorders, which may be triggered or characterized by sleep disturbances.

. Introduction Effects of sleep deprivation on neurobehavioral function (e.g., vigilance and cognition) are well documented. The prefrontal cortex (PFC) is particularly sensitive to sleep loss (Drummond et al., 1999 and Thomas et al., 2000), with corresponding impairments observed in PFC-associated executive functions (Harrison and Horne, 1998, Harrison and Horne, 1999, Jones and Harrison, 2001 and Muzur et al., 2002) and vigilance (Belenky et al., 2003 and Van Dongen et al., 2003). The adverse impact of sleep deprivation on mood and affective reactivity and regulation has been less thoroughly explored in the experimental literature. This is surprising given the role of prefrontal cortical circuits in regulating mood, particularly by inhibiting brain structures important to the generation and recognition of affect such as the amygdala (Davidson et al., 2000, Phillips et al., 2003 and Urry et al., 2006). Recent evidence suggests such processes may be impaired by sleep deprivation. In a recent neuroimaging study (Yoo et al., 2007), sleep deprived individuals demonstrated heightened amygdala reactivity to negative picture stimuli, which was also associated with reduced functional connectivity between the amygdala and the medial PFC. Mood responses to sleep deprivation are variable and at times labile. Sleep deprivation can induce giddiness, child-like behaviors, and silliness (Bliss et al., 1959 and Horne, 1993), as well as more widely recognized negative effects including dysphoria, increased irritability, and lowered frustration tolerance. The increased irritability that frequently accompanies sleep deprivation suggests that sleep-deprived individuals are highly reactive to emotional cues. These effects on mood can lead to negative consequences and impact functioning. For example, an inverse association between sleep duration and interpersonal difficulties and even violence has been observed in medical residents (Baldwin and Daugherty, 2004), and sleeping less than 8 h is associated with increased risk for adolescent suicidal behavior (Liu, 2004). Chronic sleep deprivation/restriction has also been associated with the development of psychopathology, including bipolar disorder (Kasper and Wehr, 1992, Wright, 1993 and Frank et al., 1997), pre- and post-partum psychosis (Brockington et al., 1990 and Sharma et al., 2004), and depression in both new mothers and fathers (Hiscock and Wake, 2001). However, the relationship between sleep deprivation and mood is not simple. Sleep deprivation transiently improves mood symptoms in 40–60% of individuals with clinical depression, although some patients’ symptoms worsen (Naylor et al., 1993, Wirz-Justice and Van den Hoofdakker, 1999, Giedke and Schwarzler, 2002 and Giedke et al., 2003). Previous experimental studies of chronic sleep restriction and acute sleep deprivation in healthy individuals have documented a deterioration of mood, with larger effect sizes than for either cognitive or motor responses (Pilcher and Huffcutt, 1996). However, previous studies almost exclusively used self-report outcomes. The reliability of such self-report data is uncertain due to contextual factors (e.g., reporting bias, demand characteristics, and scale interpretation). Objective measures of affective responding may help to characterize and quantify the affective consequences of sleep deprivation. Ultimately, such information may help to uncover pathways by which sleep is related to affective impairments and the development of mood disorders. For instance, sleep deprivation may be associated with disruptions in the dynamic time-course of responses to cognitive and emotional information as seen in depression (Challis and Krane, 1988, Deldin et al., 2001, Siegle et al., 2001, Siegle et al., 2002, Siegle et al., 2003a, Siegle et al., 2003b, Siegle et al., 2007 and Wagner et al., 2006). Self-report measures cannot capture this information, which occurs on the time-scale of milliseconds or seconds. In this study, we used pupillary response as an indicator of cognitive and emotional information processing in order to examine the magnitude and time-course of responses to affective picture stimuli in healthy adults following sleep deprivation or normal sleep. We used pupillography for several reasons. First, as there is extensive overlap between cognitive and affective processes (e.g., Davidson, 2003) it is appropriate that pupillary responses reflect each of these phenomena. Many studies have demonstrated pupil dilation to be a reliable correlate of cognitive load. For example, the pupil dilates more under conditions of higher attentional allocation, memory use, or interpretation of more difficult material (see Beatty, 1982 and Steinhauer and Hakerem, 1992 for reviews). The pupil has also been shown to dilate in response to emotional information (Janisse, 1974 and Bradley et al., 2008). Second, sustained cognitive load leads to sustained pupil dilation (Beatty, 1982). Thus, pupillography is an appropriate measure to examine immediate and sustained processing of emotional information. Third, the pupil is innervated by brain structures involved in cognitive and emotional processing, such as the anterior cingulate cortex (Szabadi and Bradshaw, 1996). Stimulation of limbic regions such as the amygdala increases pupil dilation (Koikegami and Yoshida, 1953 and Fernandez De Molina and Hunsperger, 1962), as does stimulation of the midbrain reticular formation (Beatty, 1986), which receives afferent projections from the frontal cortex and sends efferent projections to the ocular motor nuclei. Concurrent pupil dilation/functional magnetic resonance imaging assessment has confirmed that pupil dilation reflects the time-course of activity in brain areas associated with cognitive processing including the dorsolateral prefrontal cortex (Siegle et al., 2003a and Siegle et al., 2003b). Urry and colleagues (2006) recently used this method to demonstrate that pupil dilation reflects the time-course of neural responses to affective picture stimuli as well as explicit instructions to regulate emotions. The pupil therefore reflects initial reactivity as well as brain processes associated with subsequent affect regulation, and aspects of arousal (Critchley et al., 2005), even though it may be difficult to distinguish specific cognitive and emotional sub-processes in a given instant. For this pilot study, we used passive viewing of visual stimuli to examine automatic reactivity to emotional stimuli (e.g., Cuthbert et al., 2000) in healthy adults following either one night of total sleep deprivation or following a night of normal sleep. A passive viewing task was employed to assess naturalistic reactivity outside the context of laboratory-induced explicit cognitive or emotional demands. We expected negative stimuli to induce larger pupillary responses than neutral or positive stimuli in the sleep deprivation condition compared to a non-sleep-deprived control group. Such data would reflect a fundamental tendency towards increased reactivity in the seconds following emotional stimuli in sleep deprivation. That said, our analysis path also allowed for the potential that sleep deprivation was associated more diffusely with increased arousal which would be evidenced by increased pupillary responses to both negative and positive stimuli compared to neutral stimuli.

Results 3.1. Behavioral performance and post-task subjective ratings There was a significant main effect of valence in subjective ratings of both pleasantness (valence) and arousal, F(2,21) = 244.1, p < 0.001 and F(2,21) = 73.4, p < 0.001, but no main effect of group, and no group by valence interaction (F's < 0.2, p's > 0.6). As expected, positive pictures were rated as more pleasant (t(22) = 13.1, p < .001) and arousing (t(22) = 8.7, p < 0.001) than neutral pictures, while negative pictures were rated as less pleasant (t(22) = 22.4, p < 0.001) and more arousing (t(22) = 10.4, p < 0.001) than neutral pictures. Negative pictures were slightly but significantly rated more arousing than positive pictures (t(22) = 2.8, p = 0.010). Subjective valence was rated from 1 (very pleasant) to 9 (very unpleasant), and subjective arousal was rated from 1 (very aroused) to 9 (very calm). Mean ± standard deviation valence ratings for positive, neutral, and negative pictures were 2.8 ± 0.8, 4.8 ± 0.2, and 7.6 ± 0.2, respectively; arousal ratings for positive, neutral, and negative pictures were 5.2 ± 1.7, 7.4 ± 1.3, and 4.3 ± 1.3, respectively. These results suggest that sleep deprivation did not impact subjective ratings. There were no significant findings in the reaction time data (F's < 2.1, p's > 0.15), suggesting that the sleep-deprived individuals were as engaged in the task as the non-deprived controls. 3.2. Pupillary responses to picture stimuli Light-reflex corrected pupillary waveform averages for the non-SD and SD groups are shown in Fig. 1. Mixed effects analysis revealed a significant group × valence × time interaction, F(54,1695.8) = 1.47, p = .015. In other words, the SD and non-SD groups had different pupillary responses to specific valenced stimuli. To clarify the nature of this interaction, separate sets of ANOVA analyses were performed for the SD and non-SD groups, as well as comparing each valence between the two groups. Light-reflex corrected pupillary waveform averages during trials of positive, ... Fig. 1. Light-reflex corrected pupillary waveform averages during trials of positive, negative, and neutral pictures for the non-SD (left) and SD (right) groups. The regions immediately below the x-axis highlighted in gray (dark gray, p < .05; light gray, p < .10) show where the effect of valence was significant within-groups. Between-group differences are highlighted in gray further below the x-axis, first for negative stimuli during the cue (a), and below that for neutral stimuli during the inter-stimulus interval (b). Highlighted sections that are depicted with bars above them are the regions that were long enough for the entire window to be considered statistically significant at p < .05 using the Guthrie and Buchwald (1991) method of type-I error control. Figure options For the SD group, a contiguous window during the stimulus presentation was significant from 3.55 to 6.07 s (relative to cue onset), F(2,13) = 11.82, p = 0.001. Responses in this window were larger for negative pictures (mean ± standard deviation, M = 0.037 mm ± 0.029) compared to both positive (M = −0.023 mm ± 0.052) and neutral (M = −0.015 ± 0.055) pictures, t(14) = 3.66, p = 0.003, d = 0.94 and t(14) = 2.77, p = 0.015, d = 0.72, respectively. For the non-SD group, differential responses to the valences were apparent from 3.02 to 4.33 s, F(2,13) = 5.73, p = 0.016. Pupillary responses in this window were smaller for positive pictures (M = −0.042 mm ± 0.045) compared to both negative (M = 0.029 mm ± 0.054) and neutral (M = 0.013 mm ± 0.044), t(14) = 3.07, p = 0.008, d = 0.79 and t(14) = 2.91, p = 0.011, d = 0.75, respectively. Although the non-SD group had larger responses to negative stimuli than neutral and positive stimuli during the second half of the stimulus presentation period, there were no regions long enough to be considered statistically significant. We also examined differences between the SD and non-SD groups for each valence separately. Compared to the non-SD group, the SD group had significantly larger responses from 0.25 to 0.77 s of the warning cue during blocks of negative stimuli, indicating anticipatory reactivity (t(28) = 2.04, p = 0.05, d = 0.75, SD group M = 0.011 mm ± 0.022, non-SD group M = −0.006 ± 0.023). This difference is illustrated in Fig. 1 by an elevated waveform for negative stimuli in the “cue” region in the SD group compared to the non-SD group. To examine how the anticipatory response developed over time, we compared the average response within this window for each of the three blocks of negative trials (five stimuli per block) with a 2 (group) by 3 (blocks) repeated measures ANOVA. As expected, the ANOVA revealed a significant main effect of group, where the SD group had larger responses overall (F(1,28) = 4.76, p = 0.038), and a significant group by block interaction, F(2,56) = 4.04, p = 0.023. Post hoc independent samples t-tests revealed that the SD group had significantly larger responses than the non-SD group only during block 2 (t(28) = 2.87, p = 0.008), but not for blocks 1 or 3 (p's > 0.36). The SD group also had larger responses during the inter-stimulus interval following neutral trials, from 8.90 to 9.58 (t(28) = 2.03, p = 0.05, d = 0.74, SD group M = 0.029 mm ± 0.084, non-SD group M = −0.021 ± 0.043) and from 9.62 to 10.33 s (t(28) = 1.90, p = 0.07, d = 0.70, SD group M = 0.029 mm ± 0.065, non-SD group M = -0.013 ± 0.057). This is illustrated in Fig. 1 by an elevated waveform to neutral stimuli during the inter-stimulus interval for the SD group compared to the non-SD group. There were no significant group differences during trials of positive stimuli.