Peter L. Franzen

A Developmental Functional MRI Study of Spatial Working Memory

Functional magnetic resonance imaging (fMRI) was used to examine patterns of cortical activity in children during performance of a spatial working memory task. Six children (8-10 years) and six adults (19-26 years) searched a linear array of four boxes for the appearance of a dot. In the visual blocks, participants made no response. In the motor blocks, participants were instructed to indicate the location of the dot on each trial using a button-press response. In the working memory blocks, participants were instructed to indicate at which location the dot had appeared 1 or 2 trials previously. Both children and adults showed activity in the left precentral and postcentral gyri, as well as the right cerebellum for the motor condition as compared to the visual condition. Comparison of the memory and motor conditions revealed reliable activity in the right superior frontal gyrus (BA 8), right dorsolateral prefrontal cortex (BA 10/46), right superior parietal cortex, and bilateral inferior parietal cortex for both adults and children. These results suggest that spatial working memory tasks activate very similar cortical regions for school-age children and adults. The findings differ from previous imaging studies of nonspatial working memory tasks in that the prefrontal activations observed in the current work tend to be more dorsal. Results are discussed in light of the significant behavioral performance differences observed between child and adult participants.

Efficacy of Brief Behavioral Treatment for Chronic Insomnia in Older Adults

BACKGROUND Chronic insomnia is a common health problem with substantial consequences in older adults. Cognitive behavioral treatments are efficacious but not widely available. The aim of this study was to test the efficacy of brief behavioral treatment for insomnia (BBTI) vs an information control (IC) condition. METHODS A total of 79 older adults (mean age, 71.7 years; 54 women [70%]) with chronic insomnia and common comorbidities were recruited from the community and 1 primary care clinic. Participants were randomly assigned to either BBTI, consisting of individualized behavioral instructions delivered in 2 intervention sessions and 2 telephone calls, or IC, consisting of printed educational material. Both interventions were delivered by a nurse clinician. The primary outcome was categorically defined treatment response at 4 weeks, based on sleep questionnaires and diaries. Secondary outcomes included self-report symptom and health measures, sleep diaries, actigraphy, and polysomnography. RESULTS Categorically defined response (67% [n = 26] vs 25% [n = 10]; χ(2) = 13.8) (P < .001) and the proportion of participants without insomnia (55% [n = 21] vs 13% [n = 5]; χ(2) = 15.5) (P < .001) were significantly higher for BBTI than for IC. The number needed to treat was 2.4 for each outcome. No differential effects were found for subgroups according to hypnotic or antidepressant use, sleep apnea, or recruitment source. The BBTI produced significantly better outcomes in self-reported sleep and health (group × time interaction, F(5,73) = 5.99, P < .001), sleep diary (F(8,70) = 4.32, P < .001), and actigraphy (F(4,74) = 17.72, P < .001), but not polysomnography. Improvements were maintained at 6 months. CONCLUSION We found that BBTI is a simple, efficacious, and durable intervention for chronic insomnia in older adults that has potential for dissemination across medical settings. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00177203.

Relationships between affect, vigilance, and sleepiness following sleep deprivation

This pilot study examined the relationships between the effects of sleep deprivation on subjective and objective measures of sleepiness and affect, and psychomotor vigilance performance. Following an adaptation night in the laboratory, healthy young adults were randomly assigned to either a night of total sleep deprivation (SD group; n = 15) or to a night of normal sleep (non‐SD group; n = 14) under controlled laboratory conditions. The following day, subjective reports of mood and sleepiness, objective sleepiness (Multiple Sleep Latency Test and spontaneous oscillations in pupil diameter, PUI), affective reactivity/regulation (pupil dilation responses to emotional pictures), and psychomotor vigilance performance (PVT) were measured. Sleep deprivation had a significant impact on all three domains (affect, sleepiness, and vigilance), with significant group differences for eight of the nine outcome measures. Exploratory factor analyses performed across the entire sample and within the SD group alone revealed that the outcomes clustered on three orthogonal dimensions reflecting the method of measurement: physiological measures of sleepiness and affective reactivity/regulation, subjective measures of sleepiness and mood, and vigilance performance. Sleepiness and affective responses to sleep deprivation were associated (although separately for objective and subjective measures). PVT performance was also independent of the sleepiness and affect outcomes. These findings suggest that objective and subjective measures represent distinct entities that should not be assumed to be equivalent. By including affective outcomes in experimental sleep deprivation research, the impact of sleep loss on affective function and their relationship to other neurobehavioral domains can be assessed.

Sensitivity of prefrontal cortex to changes in target probability: A functional MRI study

Electrophysiological studies suggest sensitivity of the prefrontal cortex to changes in the probability of an event. The purpose of this study was to determine if subregions of the prefrontal cortex respond differentially to changes in target probabilities using functional magnetic resonance imaging (fMRI). Ten right‐handed adults were scanned using a gradient‐echo, echo planar imaging sequence during performance of an oddball paradigm. Subjects were instructed to respond to any letter but “X”. The frequency of targets (i.e., any letter but X) varied across trials. The results showed that dorsal prefrontal regions were active during infrequent events and ventral prefrontal regions were active during frequent events. Further, we observed an inverse relation between the dorsal and ventral prefrontal regions such that when activity in dorsal prefrontal regions increased, activity in ventral prefrontal regions decreased, and vice versa. This finding may index competing cognitive processes or capacity limitations. Most importantly, these findings taken as a whole suggest that any simple theory of prefrontal cortex function must take into account the sensitivity of this region to changes in target probability. Hum. Brain Mapping 13:26–33, 2001.

Sleep deprivation alters pupillary reactivity to emotional stimuli in healthy young adults.

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.

Night-to-night sleep variability in older adults with and without chronic insomnia.

OBJECTIVES (1) To quantify night-to-night variability in sleep behaviors and sleep measures among older chronic insomnia (CI) subjects and non-insomnia (NI) controls; (2) to investigate systematic temporal patterns of sleep behaviors and sleep measures across nights; and (3) to examine clinical correlates of sleep variability. METHODS Sixty-one older adults with CI (71.4years old, 67% F) and 31 older adults with NI (70.7years old, 65% F) completed questionnaires, kept sleep diaries and wore wrist actigraphs for 2 weeks. Mixed models were used to estimate within-subject mean and standard deviation values; these were then compared across groups. Mixed models were also used to determine associations across nights of sleep measures. RESULTS CI and NI differed on mean values for clinical ratings and sleep diary measures, but not for actigraphy measures. CI also showed significantly greater variability than NI on most sleep diary measures and on actigraphically measured wakefulness after sleep onset (WASO) and sleep efficiency. Among CI, neither diary nor actigraphy measures from one night correlated with values from the previous night. Diary WASO, sleep time, actigraphy sleep latency and sleep time, however, positively correlated with values from the previous two nights. Variability measures were not correlated with other global clinical measures among CI. CONCLUSIONS Compared to NI, older adults with CI report worse sleep and greater night-to-night variability, which was confirmed with actigraphy. There was little evidence for positive or negative correlation of sleep measures across nights. Variability of sleep may be an important target for insomnia treatments.

Cardiovascular reactivity to acute psychological stress following sleep deprivation.

Objective: Psychological stress and sleep disturbances are highly prevalent and are both implicated in the etiology of cardiovascular diseases. Given the common co-occurrence of psychological distress and sleep disturbances including short sleep duration, this study examined the combined effects of these two factors on blood pressure reactivity to immediate mental challenge tasks after well-rested and sleep-deprived experimental conditions. Methods: Participants (n = 20) were healthy young adults free from current or past sleep, psychiatric, or major medical disorders. Using a within-subjects crossover design, we examined acute stress reactivity under two experimental conditions: after a night of normal sleep in the laboratory and after a night of total sleep deprivation. Two standardized psychological stress tasks were administered, a Stroop color-word naming interference task and a speech task, which were preceded by a prestress baseline period and followed by a poststress recovery period. Each period was 10 minutes in duration, and blood pressure recordings were collected every 2.5 minutes throughout each period. Mean blood pressure responses during stress and recovery periods were examined with a mixed-effects analysis of covariance, controlling for baseline blood pressure. Results: There was a significant interaction between sleep deprivation and stress on systolic blood pressure (F(2,82.7) = 4.05, p = .02). Systolic blood pressure was higher in the sleep deprivation condition compared with the normal sleep condition during the speech task and during the two baseline periods. Conclusions: Sleep deprivation amplified systolic blood pressure increases to psychological stress. Sleep loss may increase cardiovascular risk by dysregulating stress physiology.

Poor sleep quality predicts onset of either major depression or subsyndromal depression with irritability during interferon-alpha treatment

Major depressive disorder (MDD) often occurs during pegylated IFN-alpha2 (IFN-alpha) treatment. Identifying who is at risk for MDD in this population is essential, and epidemiological studies suggest that sleep may be related to depression risk. Controlling for pre-existing depression symptoms, we therefore examined whether sleep quality prior to IFN-alpha treatment would predict subsequent MDD incidence during IFN-alpha treatment. Adults with hepatitis C but without current clinical MDD (n=86) were evaluated prior to IFN-alpha treatment and then prospectively monitored during treatment using self-report measures of sleep quality (PSQI), depression (BDI), and anger and irritability (AIAQ), as well as with Structured Clinical Interviews for DSM-IV Axis I Disorders (SCID-I). During IFN-alpha treatment, 19% developed MDD, 19% developed subsyndromal depression with irritability, and one developed mania. Controlling for baseline depression symptoms and past history of depression, patients with worse sleep quality (PSQI > or = 10) prior to treatment had a significantly shorter time until they developed MDD or any severe psychiatric problem. These findings may have important implications for understanding, predicting, and possibly preventing depression, particularly in individuals treated with IFN-alpha.

The post illumination pupil response is reduced in seasonal affective disorder

Individuals with seasonal affective disorder (SAD) may have a decreased retinal sensitivity in the non-image forming light-input pathway. We examined the post illumination pupil response (PIPR) among individuals with SAD and healthy controls to identify possible differences in the melanopsin signaling pathway. We also investigated whether melanopsin gene (OPN4) variations would predict variability in the PIPR. Fifteen SAD and 15 control participants (80% women, mean age 36.7 years, S.D.=14.5) were assessed in the fall/winter. Participants were diagnosed based on DSM-IV-TR criteria. Infrared pupillometry was used to measure pupil diameter prior to, during, and after red and blue stimuli. In response to blue light, the SAD group had a reduced PIPR and a lower PIPR percent change relative to controls. The PIPR after the blue stimulus also varied on the basis of OPN4 I394T genotype, but not OPN4 P10L genotype. These findings may indicate that individuals with SAD have a less sensitive light input pathway as measured by the PIPR, leading to differences in neurobiological and behavioral responses such as alertness, circadian photoentrainment, and melatonin release. In addition, this sensitivity may vary based on sequence variations in OPN4, although a larger sample and replication is needed.

Sleep deprivation amplifies striatal activation to monetary reward

BACKGROUND Sleep loss produces abnormal increases in reward seeking but the mechanisms underlying this phenomenon are poorly understood. The present study examined the influence of one night of sleep deprivation on neural responses to a monetary reward task in a sample of late adolescents/young adults. METHOD Using a within-subjects crossover design, 27 healthy, right-handed late adolescents/young adults (16 females, 11 males; mean age 23.1 years) underwent functional magnetic resonance imaging (fMRI) following a night of sleep deprivation and following a night of normal sleep. Participants’ recent sleep history was monitored using actigraphy for 1 week prior to each sleep condition. RESULTS Following sleep deprivation, participants exhibited increased activity in the ventral striatum (VS) and reduced deactivation in the medial prefrontal cortex (mPFC) during the winning of monetary reward, relative to the same task following normal sleep conditions. Shorter total sleep time over the five nights before the sleep-deprived testing condition was associated with reduced deactivation in the mPFC during reward. CONCLUSIONS These findings support the hypothesis that sleep loss produces aberrant functioning in reward neural circuitry, increasing the salience of positively reinforcing stimuli. Aberrant reward functioning related to insufficient sleep may contribute to the development and maintenance of reward dysfunction-related disorders, such as compulsive gambling, eating, substance abuse and mood disorders.