**5. Influence of sleep loss due to partial deprivation of a night's sleep on individual differences in working memory performance**

#### **5.1 Working memory performance**

As already noted in Section 3 concerning the effects of sleep loss on cognition, a discrepancy in the effects that sleep loss has on behavioral performance compared with the effects it has on neural activity has been reported in relation to working memory performance; sleep loss does not deteriorate behavioral performance itself, but rather the neural activity associated with the behavior. Possible interindividual differences in the vulnerability to sleep loss of executive functions, which also play crucial roles in working memory processing, have also been suggested. We explored this issue in a second study using NIRS (Honma et al., 2010).

### **5.2 Study design**

30 Infrared Spectroscopy – Life and Biomedical Sciences

Fig. 4. Sleep deprivation attenuates short-time perception the following morning

**4.5 Influence of the PFC's vulnerability to sleep loss on short-time perception** 

the SD condition is clearly attenuated.

channels 17, 21, and 22 (Fig. 5).

It was previously shown that a short-time perception profile exhibits diurnal variation, reaching a peak (the longest produced time) around 09:00 and a nadir (the shortest produced time) around 21:00 with a regular sleep-wake cycle under experimental conditions (Kuriyama et al., 2005). Taken together, circadian oscillation in short-time perception under

Oxy-Hb concentration measured by NIRS suggested that PFC activity in the SD condition, compared with that in the SC condition, was more enhanced in the left hemisphere on day 2. Moreover, enhanced oxy-Hb concentration changes on day 2 in the SD condition, compared with those in the SC condition, were observed in the LAPFC region of interest (ROI) at

Fig. 5. Left anterior PFC activity during the TP task was enhanced after sleep deprivation

A functional correlation was observed between increased activation of the LAPFC after sleep deprivation and short-time perception, although unlike in previous studies Fifty-five healthy university students (26 males, 29 females) participated in the study. Subjects, who regularly slept 7–9 h in a night, participated in an overnight experiment in a laboratory setting, starting at 22:00 on day 1 and finishing at 10:00 on day 2. Subjects were deprived an average of 2.32 h (29.5%) of sleep by experimental manipulation. Subjects retired to bed at 01:00 in the laboratory and were forcibly awakened at 07:00 am.

A visual *n*-back working memory (WM) task (Callicott et al., 1998, 1999; Gevins & Cutillo, 1993; Kuriyama et al., 2008) with two separate load levels was utilized. For the 0-back task (low-load WM task), subjects had to respond whenever a single-digit number appeared on a screen. For the 2-back task (high-load WM task), they had to press a button on the right when the single-digit number on the screen was identical to that which had appeared last

Effects of Sleep Debt on Cognitive Performance and Prefrontal Activity in Humans 33

**5.4 Influence of the PFC's vulnerability to sleep loss on working memory performance**  Twelve of the 55 subjects showed overnight decrements in alertness level as reflected by an increased SSS level (average: 1.41, SD: 0.41), while conversely 17 showed overnight decrements reflected by a decreased SSS level (average: 21.29, SD: 0.49), and 26 showed no change in alertness level. The change in alertness level was negatively correlated with RT on the 2-back task, but not on the 0-back task (Fig. 7), and the change in SSS was not correlated

Fig. 7. Correlation of overnight change in alertness level with that in WM performance

better performance not on the low-load WM task but on the high-load WM task.

Although the subjects had similar sleep-wake habits in daily life and they experienced the same restricted sleep duration on the experimental night, alertness was increased in some subjects but was decreased in others during the WM tasks. This suggests that subjects who improved their alertness—who may have better abilities to overcome sleepiness—showed

**5.5 Relationship between the PFC's vulnerability to sleep loss and working memory** 

At every channel in the bilateral PFC region, differences in the change in oxy-Hb concentration between the 2- and 0-back tasks positively correlated with overnight change in alertness (Fig. 8), which is in line with previous neuroimaging studies using fMRI (Cohen et al., 1997; Owen et al., 1998) and PET (Owen et al., 1996; Sweeney et al., 1996). On the other hand, change in oxy-Hb concentration in the bilateral PFC region on the 2-back task for some channels (channels 5, 10, 13, and 18) positively correlated with overnight change in alertness (Fig. 9 left), while change on the 0-back task for some channels (channels 10 and 15) in the right PFC region negatively correlated with overnight change in alertness (Fig. 9

The activity in the right prefrontal site corresponding to channel 10 showed an opposite pattern between the 2- and 0-back tasks (Fig. 10), suggesting the ability to conquer sleepiness. This ability might contribute to the function of providing sufficient activity to

with %CR regardless of the task difficulty.

**processing difficulties** 

right).

but one, otherwise to press the button on the left. Each level of task was run in blocks of 12+n stimuli and was conducted two times; thus, 24 responses were obtained at each load level. Average response times (RTs) and correct response rates (%CRs) were evaluated.

Alertness level was evaluated immediately before and after the experiment using the Stanford Sleepiness Scale (SSS; Hoddes et al., 1971). The SSS consists of a 7-point scale ranging from level 1 (feeling active, vital, alert, or wide awake) to level 7 (no longer fighting sleep). Subjects selected the most appropriate level to reflect their present state of alertness. To assess individual ability to overcome sleepiness during WM tasks, change in SSS level was individually calculated by subtracting the post-experiment SSS score from the preexperiment SSS score.

#### **5.3 NIRS recording and data analysis**

Regional hemodynamic changes in brain tissue were monitored throughout the TP sessions by a continuous wave-type NIRS system (ETG-100, Hitachi Medical Co., Tokyo, Japan: Fig. 6), which outputs near-infrared light at two wavelengths (780 and 830 nm). Oxy- and deoxy-Hb concentrations were measured in a manner similar to the short-time perception study (Soshi et al., 2010) described in the preceding section [section 4.3].

Fig. 6. Optical Topography System ETG-100 (Hitachi Medical Co., Tokyo, Japan)

We analyzed oxy-Hb data as a reflection of event-related responses in the PFC. The continuous oxy-Hb data were filtered with band-pass frequencies in the range of 0.01–0.2 Hz and were standardized (z-score). Changes in oxy-Hb concentration time-locked to experimental blocks consisting of 12 trials were extracted for each experimental condition 1000 ms before the onset of the trial block (baseline) to 4400 ms after the onset (2400 ms for the 12-trial duration and 2000 ms for the post-trial interval). Baseline correction of the changes in oxy-Hb concentration was performed utilizing the mean z-scores of 1000 ms prior to the onset of the experimental blocks before individual averaging. Mean z-scores of the changes in oxy-Hb concentration during the 4400 ms period after the beginning of the trial block were utilized for subsequent statistical analysis.

but one, otherwise to press the button on the left. Each level of task was run in blocks of 12+n stimuli and was conducted two times; thus, 24 responses were obtained at each load level. Average response times (RTs) and correct response rates (%CRs) were evaluated.

Alertness level was evaluated immediately before and after the experiment using the Stanford Sleepiness Scale (SSS; Hoddes et al., 1971). The SSS consists of a 7-point scale ranging from level 1 (feeling active, vital, alert, or wide awake) to level 7 (no longer fighting sleep). Subjects selected the most appropriate level to reflect their present state of alertness. To assess individual ability to overcome sleepiness during WM tasks, change in SSS level was individually calculated by subtracting the post-experiment SSS score from the pre-

Regional hemodynamic changes in brain tissue were monitored throughout the TP sessions by a continuous wave-type NIRS system (ETG-100, Hitachi Medical Co., Tokyo, Japan: Fig. 6), which outputs near-infrared light at two wavelengths (780 and 830 nm). Oxy- and deoxy-Hb concentrations were measured in a manner similar to the short-time perception study

(Soshi et al., 2010) described in the preceding section [section 4.3].

Fig. 6. Optical Topography System ETG-100 (Hitachi Medical Co., Tokyo, Japan)

trial block were utilized for subsequent statistical analysis.

We analyzed oxy-Hb data as a reflection of event-related responses in the PFC. The continuous oxy-Hb data were filtered with band-pass frequencies in the range of 0.01–0.2 Hz and were standardized (z-score). Changes in oxy-Hb concentration time-locked to experimental blocks consisting of 12 trials were extracted for each experimental condition 1000 ms before the onset of the trial block (baseline) to 4400 ms after the onset (2400 ms for the 12-trial duration and 2000 ms for the post-trial interval). Baseline correction of the changes in oxy-Hb concentration was performed utilizing the mean z-scores of 1000 ms prior to the onset of the experimental blocks before individual averaging. Mean z-scores of the changes in oxy-Hb concentration during the 4400 ms period after the beginning of the

experiment SSS score.

**5.3 NIRS recording and data analysis** 

#### **5.4 Influence of the PFC's vulnerability to sleep loss on working memory performance**

Twelve of the 55 subjects showed overnight decrements in alertness level as reflected by an increased SSS level (average: 1.41, SD: 0.41), while conversely 17 showed overnight decrements reflected by a decreased SSS level (average: 21.29, SD: 0.49), and 26 showed no change in alertness level. The change in alertness level was negatively correlated with RT on the 2-back task, but not on the 0-back task (Fig. 7), and the change in SSS was not correlated with %CR regardless of the task difficulty.

Fig. 7. Correlation of overnight change in alertness level with that in WM performance

Although the subjects had similar sleep-wake habits in daily life and they experienced the same restricted sleep duration on the experimental night, alertness was increased in some subjects but was decreased in others during the WM tasks. This suggests that subjects who improved their alertness—who may have better abilities to overcome sleepiness—showed better performance not on the low-load WM task but on the high-load WM task.

#### **5.5 Relationship between the PFC's vulnerability to sleep loss and working memory processing difficulties**

At every channel in the bilateral PFC region, differences in the change in oxy-Hb concentration between the 2- and 0-back tasks positively correlated with overnight change in alertness (Fig. 8), which is in line with previous neuroimaging studies using fMRI (Cohen et al., 1997; Owen et al., 1998) and PET (Owen et al., 1996; Sweeney et al., 1996). On the other hand, change in oxy-Hb concentration in the bilateral PFC region on the 2-back task for some channels (channels 5, 10, 13, and 18) positively correlated with overnight change in alertness (Fig. 9 left), while change on the 0-back task for some channels (channels 10 and 15) in the right PFC region negatively correlated with overnight change in alertness (Fig. 9 right).

The activity in the right prefrontal site corresponding to channel 10 showed an opposite pattern between the 2- and 0-back tasks (Fig. 10), suggesting the ability to conquer sleepiness. This ability might contribute to the function of providing sufficient activity to

Effects of Sleep Debt on Cognitive Performance and Prefrontal Activity in Humans 35

match the demands of a task. In other words, the cortical activity corresponding to channel 10 susceptibly escalates with changes in both alertness and cognitive load, thereby achieving better performance. This site in the right PFC might therefore be related to the ability to

**5.6 Relation between individual differences in the ability to conquer sleepiness during** 

We next explored the relationship between activity in the right prefrontal site corresponding to channel 10 and individual personality traits. We assessed personality traits using the revised version of the Neuroticism-Extroversion-Openness Personality Inventory (NEO PI-R) and the Revised Temperament and Character Inventory (TCI, Version 9). NEO PI-R is a 240-item measure of the Five Factor Model: Neuroticism, Extraversion, Openness to experience, Agreeableness, and Conscientiousness (Costa & McCrae, 1995). The TCI, too, is a 240-item measure of the seven dimensions of personality traits: Novelty seeking, Harm avoidance, Reward dependence, Persistence, Self-directedness, Cooperativeness, and Selftranscendence (Cloninger, 1987). Both of these inventories are widely used in biological correlational research in a variety of fields, including psychiatric diagnosis (Cloninger, 1990; Frokjaer et al., 2008), behavior (Grucza et al., 2006; Saggino & Balsamo, 2003), genotyping (Cloninger, 2002; Strobel et al., 2003), and brain activities (Baeken et al., 2009; Villafuerte et

We identified several personality traits that correlated with a difference in activity change between the 2- and 0-back tasks at channel 10. For instance, Neuroticism on the NEO PI-R was positively correlated and Self-directedness on the TCI negatively correlated with a difference in change in oxy-Hb concentration between the two tasks (Yoshiike, Honma & Kuriyama, in preparation). This finding suggests that a stronger tendency for neuroticism and a weaker one for self-directedness may lead to successful performance under sleep loss conditions. Greater neuroticism is sometimes associated with psychiatric problems such as depression or anxiety (Strobel et al., 2003), which reflect poor stress coping mechanisms like avoidance (Andrews et al., 2010). However, within a healthy range, a trait of neuroticism may be beneficial to conquering sleepiness. Moreover, although the concept of selfdirectedness is based on the "power of will" (i.e., the ability to control oneself to serve the purpose of one's own will), greater self-directedness may, surprisingly, result in succumbing to sleepiness. Chronic insomniacs showed greater neuroticism (van de Laar et al., 2010) and less self-directedness (de Saint Hilaire et al., 2005), suggesting that problems in

When the ROI is compatible with the strengths of NIRS, the technique is valuable for investigating human frontal functioning associated with deteriorated cognition caused by sleep loss. Indeed, our studies demonstrated that certain functional differences in the

We can sum up by saying the PFC mediates various cognitive functions, from basic functions such as simple response to stimulus and time perception to higher functions such as working memory including executive functions, to orchestrate perception, memory,

bilateral PFC under sleep loss conditions correspond to certain cognitive tasks.

the right PFC might be associated with the symptoms of insomnia.

conquer sleepiness with cognitive performance.

al., 2011).

**6. Conclusion** 

**working memory processing and personality traits** 

Fig. 8. Significant positive correlation between changes in oxy-Hb concentration and alertness for the difference between the 2- and 0-back tasks

Fig. 9. Correlation between changes in oxy-Hb concentration and alertness on the 2-back task (left panel) and 0-back task (right panel)

Fig. 10. Correlation between changes in oxy-Hb concentration and alertness on the 2- and 0 back tasks for channel 10

match the demands of a task. In other words, the cortical activity corresponding to channel 10 susceptibly escalates with changes in both alertness and cognitive load, thereby achieving better performance. This site in the right PFC might therefore be related to the ability to conquer sleepiness with cognitive performance.

#### **5.6 Relation between individual differences in the ability to conquer sleepiness during working memory processing and personality traits**

We next explored the relationship between activity in the right prefrontal site corresponding to channel 10 and individual personality traits. We assessed personality traits using the revised version of the Neuroticism-Extroversion-Openness Personality Inventory (NEO PI-R) and the Revised Temperament and Character Inventory (TCI, Version 9). NEO PI-R is a 240-item measure of the Five Factor Model: Neuroticism, Extraversion, Openness to experience, Agreeableness, and Conscientiousness (Costa & McCrae, 1995). The TCI, too, is a 240-item measure of the seven dimensions of personality traits: Novelty seeking, Harm avoidance, Reward dependence, Persistence, Self-directedness, Cooperativeness, and Selftranscendence (Cloninger, 1987). Both of these inventories are widely used in biological correlational research in a variety of fields, including psychiatric diagnosis (Cloninger, 1990; Frokjaer et al., 2008), behavior (Grucza et al., 2006; Saggino & Balsamo, 2003), genotyping (Cloninger, 2002; Strobel et al., 2003), and brain activities (Baeken et al., 2009; Villafuerte et al., 2011).

We identified several personality traits that correlated with a difference in activity change between the 2- and 0-back tasks at channel 10. For instance, Neuroticism on the NEO PI-R was positively correlated and Self-directedness on the TCI negatively correlated with a difference in change in oxy-Hb concentration between the two tasks (Yoshiike, Honma & Kuriyama, in preparation). This finding suggests that a stronger tendency for neuroticism and a weaker one for self-directedness may lead to successful performance under sleep loss conditions. Greater neuroticism is sometimes associated with psychiatric problems such as depression or anxiety (Strobel et al., 2003), which reflect poor stress coping mechanisms like avoidance (Andrews et al., 2010). However, within a healthy range, a trait of neuroticism may be beneficial to conquering sleepiness. Moreover, although the concept of selfdirectedness is based on the "power of will" (i.e., the ability to control oneself to serve the purpose of one's own will), greater self-directedness may, surprisingly, result in succumbing to sleepiness. Chronic insomniacs showed greater neuroticism (van de Laar et al., 2010) and less self-directedness (de Saint Hilaire et al., 2005), suggesting that problems in the right PFC might be associated with the symptoms of insomnia.
