Arvid Morell

Acute Sleep Deprivation Enhances the Brain's Response to Hedonic Food Stimuli: An fMRI Study

CONTEXT There is growing recognition that a large number of individuals living in Western society are chronically sleep deprived. Sleep deprivation is associated with an increase in food consumption and appetite. However, the brain regions that are most susceptible to sleep deprivation-induced changes when processing food stimuli are unknown. OBJECTIVE Our objective was to examine brain activation after sleep and sleep deprivation in response to images of food. INTERVENTION Twelve normal-weight male subjects were examined on two sessions in a counterbalanced fashion: after one night of total sleep deprivation and one night of sleep. On the morning after either total sleep deprivation or sleep, neural activation was measured by functional magnetic resonance imaging in a block design alternating between high- and low-calorie food items. Hunger ratings and morning fasting plasma glucose concentrations were assessed before the scan, as were appetite ratings in response to food images after the scan. MAIN OUTCOME MEASURES Compared with sleep, total sleep deprivation was associated with an increased activation in the right anterior cingulate cortex in response to food images, independent of calorie content and prescan hunger ratings. Relative to the postsleep condition, in the total sleep deprivation condition, the activation in the anterior cingulate cortex evoked by foods correlated positively with postscan subjective appetite ratings. Self-reported hunger after the nocturnal vigil was enhanced, but importantly, no change in fasting plasma glucose concentration was found. CONCLUSIONS These results provide evidence that acute sleep loss enhances hedonic stimulus processing in the brain underlying the drive to consume food, independent of plasma glucose levels. These findings highlight a potentially important mechanism contributing to the growing levels of obesity in Western society.

Menstrual cycle effects on amygdala reactivity to emotional stimulation in premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) with luteal phase related anxiety and mood swings compromise quality of life in around 4% of reproductive women. While anxiety is related to amygdala function, prior studies on amygdala reactivity both in healthy controls and women with PMDD are inconsistent with respect to menstrual cycle effects. Here women with PMDD and healthy controls were exposed to emotional faces during the mid-follicular and late luteal phase, and mean blood-oxygen-level dependence (BOLD) signal changes in the amygdala were determined with functional magnetic resonance imaging (fMRI). Women with PMDD had enhanced bilateral amygdala reactivity in the follicular phase in comparison with healthy controls, but there was no difference between groups during the luteal phase. In contrast, healthy controls displayed higher left amygdala reactivity in the luteal than in their follicular phase. However, among women with PMDD follicular phase progesterone serum concentrations were positively correlated with bilateral amygdala reactivity while depression scores were positively correlated with right amygdala reactivity in the luteal phase. In addition, women with PMDD and high scores on trait anxiety had increased right amygdala reactivity in the luteal as compared to the follicular phase. Finally, amygdala reactivity was more prone to habituation in women with PMDD, as they had enhanced amygdala reactivity in comparison with controls at the first, but not the second scanning session. Thus, while the study failed to indicate increased luteal phase amygdala reactivity in women with PMDD, our findings suggest that anxiety proneness and progesterone levels modulate menstrual cycle related amygdala reactivity in women with PMDD.

The effect of premenstrual dysphoric disorder and menstrual cycle phase on brain activity during response inhibition

BACKGROUND Premenstrual dysphoric disorder (PMDD) has generally not been associated with impulsive behavior. However, some studies suggest that women with PMDD have higher impulsivity scores than healthy controls and that brain activity during response inhibition may vary across the menstrual cycle. Therefore, our aim was to unravel potentially important cognitive aspects of PMDD by investigating brain activity during response inhibition in women with PMDD and healthy controls in relation to menstrual cycle phase. METHODS Fourteen PMDD patients and 13 healthy controls performed a Go/NoGo task to measure brain activity during response inhibition by use of event-related functional magnetic resonance imaging. RESULTS Women with PMDD displayed decreased activity during both menstrual cycle phases compared to healthy controls in several task-related parietal areas. A significant group by phase interactions was found in the left insula, driven by enhanced activity among healthy controls in the follicular phase and by enhanced insula activity during the luteal phase among PMDD patients. LIMITATIONS The limitations of the present study are the relatively limited sample size, the relatively small number of NoGo trials and the lack of a baseline contrast for the NoGo trials. CONCLUSIONS During response inhibition women with PMDD have reduced activity in areas associated with attention and motor function which is unrelated to menstrual cycle phase. Insular cortex activity, involved in both affective and cognitive processing, was significantly activated during the luteal phase among PMDD women. These findings are relevant for the understanding of how ovarian steroids influence mood symptoms in women.

Prefrontal activity during response inhibition decreases over time in the postpartum period

The postpartum period is characterized by complex hormonal changes, but human imaging studies in the postpartum period have thus far predominantly focused on the neural correlates of maternal behavior or postpartum depression, whereas longitudinal studies on neural correlates of cognitive function across the postpartum period in healthy women are lacking. The aim of this study was to longitudinally examine response inhibition, as a measure of executive function, during the postpartum period and its neural correlates in healthy postpartum women and non-postpartum controls. Thirteen healthy postpartum women underwent event-related functional magnetic resonance imaging while performing a Go/NoGo task. The first assessment was made within 48 h of delivery, and the second at 4-7 weeks postpartum. In addition, 13 healthy women examined twice during the menstrual cycle were included as non-postpartum controls. In postpartum women region of interest analyses revealed task-related decreased activations in the right inferior frontal gyrus, right anterior cingulate, and bilateral precentral gyri at the late postpartum assessment. Generally, postpartum women displayed lower activity during response inhibition in the bilateral inferior frontal gyri and precentral gyri compared to non-postpartum controls. No differences in performance on the Go/NoGo task were found between time-points or between groups. In conclusion, this study has discovered that brain activity in prefrontal areas during a response inhibition task decreases throughout the course of the first postpartum weeks and is lower than in non-postpartum controls. Further studies on the normal adaptive brain activity changes that occur during the postpartum period are warranted.

Measurement of absolute cerebral blood flow during cardiopulmonary bypass and selective cerebral perfusion using [O-15]water and PET

Background: Competition between neurotransmitter and radioligands has provided a very useful method to assess synaptic changes in dopamine, but this approach has been slow to extend to other neurotransmitter system. Previously, Fujita and colleagues showed that the high affinity beta2-nicotinic acetylcholine receptor (b2-nAChR) radioligand [I]5-IA85380 (5-IA) may be sensitive to extracellular increases in ACh in baboons; 1 however, such an examination in humans has lagged. Given that acetylcholine is one of the major neurotransmitters in the brain and has been implicated in the psychiatric and medical illnesses, we developed a paradigm to interrogate the ACh system in vivo via use of 5-IA SPECT imaging and physostigmine, a centrally-acting acetylcholinesterase inhibitor. Methods: Six healthy subjects (3 men, 3 women; 31±4.1 yrs) participated in one 5-IA SPECT study. 5-IA was administered as a bolus plus constant infusion (B/I 7.0 h); total injected dose was 390.2±13.2 MBq. After three 30-min baseline scans at 6-8 h post infusion, physostigmine (1-1.5 mg) was administered IV over 60 min, and nine additional 30-min scans were collected during the next 6 h. The outcome measure was BPF (specific volume of distribution), calculated as VT/fp (estimated receptor availability) minus VND/fp (nondisplaceable binding; previously estimated in a smoking to satiety paradigm). Results: We observed a significant reduction in BPF after physostigmine administration (25±15% reduction in cortical regions, 15±11% thalamus (Figure 1), 16±14% in striatum, and 35±34% in cerebellum; p < .05). This effect reflected a combination of a significant decrease in tissue concentration of 5-IA (7-16% region specific, p < .05) and a significant increase in plasma parent concentration (8%, p < .05). Conclusions: These data suggest that physostigmineinduced increases in extracellular ACh might compete with 5-IA for binding to b2-nAChRs in humans, although other mechanisms, such as a direct effect of physostigmine on nicotinic acetylcholine receptors, should be ruled out. Additional validation of this paradigm is warranted, but we suggest that nicotinic imaging could be used to interrogate changes in synaptic ACh.