scholarly journals Comparable Sensitivity of Postmenopausal and Young Women to the Effects of Intranasal Insulin on Food Intake and Working Memory

2010 ◽  
Vol 31 (5) ◽  
pp. 777-777
Author(s):  
Rosemarie Krug ◽  
Christian Benedict ◽  
Jan Born ◽  
Manfred Hallschmid

ABSTRACT Context We have previously shown that enhancing brain insulin signaling by intranasal administration of a single dose of the hormone acutely reduces food intake in young men but not women, whereas its improving effects on spatial and working memory are restricted to young women. Objective Against the background of animal studies suggesting that low estrogen concentrations are a prerequisite for the anorexigenic impact of central nervous insulin, we extended our foregoing study by assessing intranasal insulin effects in postmenopausal women with comparatively low estrogen concentrations, expecting them to be more sensitive than young women to the anorexigenic effects of the hormone. Design, Setting, Participants, and Intervention In a within-subject, double-blind comparison performed at the University of Lübeck, 14 healthy postmenopausal women (body mass index, 23.71 ± 0.6 kg/m2; age, 57.61 ± 1.14 yr) were intranasally administered 160 IU regular human insulin or vehicle. Main Outcome Measures Subjects performed a working memory task (digit span) and a hippocampus-dependent visuospatial memory task. Subsequently, free-choice food intake from an ad libitum breakfast buffet was measured. Results Contrary to expectations, results in postmenopausal women mirrored those found in young women (22.44 ± 0.63 yr), i.e. insulin administration did not affect food intake (P > 0.46), but did enhance performance in the prefrontal cortex-dependent working memory task (P < 0.05). Conclusions Low estrogen levels as present in postmenopausal women do not modulate the effects of intranasal insulin in females, suggesting that in humans as opposed to rats, estrogen signaling does not critically alter central nervous system sensitivity to the effects of insulin on energy homeostasis and cognition.

2010 ◽  
Vol 95 (12) ◽  
pp. E468-E472 ◽  
Author(s):  
Rosemarie Krug ◽  
Christian Benedict ◽  
Jan Born ◽  
Manfred Hallschmid

Context: We have previously shown that enhancing brain insulin signaling by intranasal administration of a single dose of the hormone acutely reduces food intake in young men but not women, whereas its improving effects on spatial and working memory are restricted to young women. Objective: Against the background of animal studies suggesting that low estrogen concentrations are a prerequisite for the anorexigenic impact of central nervous insulin, we extended our foregoing study by assessing intranasal insulin effects in postmenopausal women with comparatively low estrogen concentrations, expecting them to be more sensitive than young women to the anorexigenic effects of the hormone. Design, Setting, Participants, and Intervention: In a within-subject, double-blind comparison performed at the University of Lübeck, 14 healthy postmenopausal women (body mass index, 23.71 ± 0.6 kg/m2; age, 57.61 ± 1.14 yr) were intranasally administered 160 IU regular human insulin or vehicle. Main Outcome Measures: Subjects performed a working memory task (digit span) and a hippocampus-dependent visuospatial memory task. Subsequently, free-choice food intake from an ad libitum breakfast buffet was measured. Results: Contrary to expectations, results in postmenopausal women mirrored those found in young women (22.44 ± 0.63 yr), i.e. insulin administration did not affect food intake (P > 0.46), but did enhance performance in the prefrontal cortex-dependent working memory task (P < 0.05). Conclusions: Low estrogen levels as present in postmenopausal women do not modulate the effects of intranasal insulin in females, suggesting that in humans as opposed to rats, estrogen signaling does not critically alter central nervous system sensitivity to the effects of insulin on energy homeostasis and cognition.


Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 5084-5084 ◽  
Author(s):  
Rosemarie Krug ◽  
Christian Benedict ◽  
Jan Born ◽  
Manfred Hallschmid

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
R. B. Silberstein ◽  
A. Pipingas ◽  
J. Song ◽  
D. A. Camfield ◽  
P. J. Nathan ◽  
...  

Ginkgo Biloba extract (GBE) is increasingly used to alleviate symptoms of age related cognitive impairment, with preclinical evidence pointing to a pro-cholinergic effect. While a number of behavioral studies have reported improvements to working memory (WM) associated with GBE, electrophysiological studies of GBE have typically been limited to recordings during a resting state. The current study investigated the chronic effects of GBE on steady state visually evoked potential (SSVEP) topography in nineteen healthy middle-aged (50-61 year old) male participants whilst completing an object WM task. A randomized double-blind crossover design was employed in which participants were allocated to receive 14 days GBE and 14 days placebo in random order. For both groups, SSVEP was recorded from 64 scalp electrode sites during the completion of an object WM task both pre- and 14 days post-treatment. GBE was found to improve behavioural performance on the WM task. GBE was also found to increase the SSVEP amplitude at occipital and frontal sites and increase SSVEP latency at left temporal and left frontal sites during the hold component of the WM task. These SSVEP changes associated with GBE may represent more efficient processing during WM task completion.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew J. Westphal ◽  
Michael E. Ballard ◽  
Nicholas Rodriguez ◽  
Taylor A. Vega ◽  
Mark D’Esposito ◽  
...  

AbstractPost-traumatic stress disorder (PTSD) leads to impairments in both cognitive and affective functioning. Animal work suggests that chronic stress reduces dopamine tone, and both animal and human studies argue that changes in dopamine tone influence working memory, a core executive function. These findings give rise to the hypothesis that increasing cortical dopamine tone in individuals with greater PTSD symptomatology should improve working memory performance. In this pharmacological functional magnetic resonance imaging (fMRI) study, 30 US military veterans exhibiting a range of PTSD severity completed an emotional working memory task. Each subject received both placebo and the catechol-O-methyl transferase inhibitor tolcapone, which increases cortical dopamine tone, in randomized, double-blind, counterbalanced fashion. Mnemonic discriminability (calculated with d′, an index of the detectability of working memory signals) and response bias were evaluated in the context of task-related brain activations. Subjects with more severe PTSD showed both greater tolcapone-mediated improvements in d′ and larger tolcapone-mediated reductions in liberally-biased responding for fearful stimuli. FMRI revealed that tolcapone augmented activity within bilateral frontoparietal control regions during the decision phase of the task. Specifically, tolcapone increased cortical responses to fearful relative to neutral stimuli in higher severity PTSD subjects, and reduced cortical responses to fearful stimuli for lower severity PTSD subjects. Moreover, tolcapone modulated prefrontal connectivity with areas overlapping the default mode network. These findings suggest that enhancing cortical dopamine tone may represent an approach to remediating cognitive and affective dysfunction in individuals with more severe PTSD symptoms.


2018 ◽  
Author(s):  
Papalini S. ◽  
Michels F. ◽  
Kohn N. ◽  
Wegman J. ◽  
van Hemert S. ◽  
...  

AbstractProbiotics are microorganisms that can provide health benefits when consumed. Recent animal studies have demonstrated that probiotics can reverse gut microbiome-related alterations in anxiety and depression-like symptoms, in hormonal responses to stress, and in cognition. However, in humans, the effects of probiotics on neurocognition remain poorly understood and a causal understanding of the gut-brain link in emotion and cognition is lacking. We aimed to fill this gap by studying the effects of a probiotics intervention versus placebo on neurocognition in healthy human volunteers.We set out to investigate the effects of a multispecies probiotic (Ecologic®Barrier) on specific neurocognitive measures of emotion reactivity, emotion regulation, and cognitive control using fMRI. Critically, we also tested whether the use of probiotics can buffer against the detrimental effects of acute stress on working memory. In a double blind, randomized, placebo-controlled, between-subjects intervention study, 58 healthy participants were tested twice, once before and once after 28 days of intervention with probiotics or placebo.Probiotics versus placebo did not affect emotion reactivity, emotion regulation, and cognitive control processes at brain or behavioral level, neither related self-report measures. However, relative to the placebo group, the probiotics group did show a significant stress-related increase in working memory performance after versus before supplementation (digit span backward, p=0.039, ηp2=.07). Interestingly, this change was associated with intervention-related neural changes in frontal cortex during cognitive control in the probiotics group, but not in the placebo group. Overall, our results show that neurocognitive effects of supplementation with a multispecies probiotic in healthy women become visible under challenging (stress) situations. Probiotics buffered against the detrimental effects of stress in terms of cognition, especially in those individuals with probiotics-induced changes in frontal brain regions during cognitive control.HighlightsWe ran a randomized placebo-controlled fMRI study with a multispecies probioticProbiotics did not affect neurocognitive measures of emotion and cognitive controlProbiotics did affect stress-related working memory and neural correlatesProbiotics in healthy individuals can support cognition under stress


2001 ◽  
Vol 7 (3) ◽  
pp. 285-293 ◽  
Author(s):  
BONNIE M. DOBBS ◽  
ALLEN R. DOBBS ◽  
IVAN KISS

Cognitive impairments are among the most frequently reported and least investigated components of the chronic fatigue syndrome (CFS). As part of a multifaceted study of the CFS, the present study investigated the cognitive functioning of chronic fatigue patients. The performance of 20 CFS patients was compared to that of controls (N = 20) on 4 tests of working memory (WM). Digit Span Forward was used to assess the storage capacity of WM. Multiple aspects of central executive functioning were assessed using several standard measures: Digit Span Backward, and Trails A and Trails B. More recently developed measures of WM were used to assess control of processing under temporal demands (working memory task) and resistance to interference (a sustained attention task). Deficits were restricted to more demanding tasks, requiring resistance to interference and efficient switching between processing routines. The overall results clearly implicate deficits in the control aspects of central executive function in CFS. (JINS, 2001, 7, 285–293.)


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Monika Pupíková ◽  
Patrik Šimko ◽  
Martin Gajdoš ◽  
Irena Rektorová

Many cognitive functions, including working memory, are processed within large-scale brain networks. We targeted the right frontoparietal network (FPN) with one session of transcranial direct current stimulation (tDCS) in an attempt to modulate the cognitive speed of a visual working memory task (WMT) in 27 young healthy subjects using a double-blind crossover design. We further explored the neural underpinnings of induced changes by performing resting-state fMRI prior to and immediately after each stimulation session with the main focus on the interaction between a task-positive FPN and a task-negative default mode network (DMN). Twenty minutes of 2 mA anodal tDCS was superior to sham stimulation in terms of cognitive speed manipulation of a subtask with processing of objects and tools in unconventional views (i.e., the higher cognitive load subtask of the offline WMT). This result was linked to the magnitude of resting-state functional connectivity decreases between the stimulated FPN seed and DMN seeds. We provide the first evidence for the action reappraisal mechanism of object and tool processing. Modulation of cognitive speed of the task by tDCS was reflected by FPN-DMN cross-talk changes.


2019 ◽  
Author(s):  
Hendrik Hartmann ◽  
Larissa K. Pauli ◽  
Lieneke K. Janssen ◽  
Sebastian Huhn ◽  
Uta Ceglarek ◽  
...  

AbstractObesity is associated with alterations in dopaminergic transmission and cognitive function. Recent findings from rodent studies suggest that diets rich in saturated fat and refined sugars (HFS) induce changes in the dopamine system independent of excessive body weight. However, so far the impact of HFS on the human brain has not been investigated. Here, we compared the effect of dietary dopamine depletion on dopamine dependent cognitive tasks between two groups that differ in habitual intake of dietary fat and sugar. Specifically, we used a double-blind within-subject crossover design to compare the effect of acute phenylalanine/tyrosine depletion (APTD) on a reinforcement learning and a working memory task, in two groups that are on opposite ends of the spectrum of self-reported HFS intake (low vs. high intake: LFS vs. HFS group). We tested 31 healthy young women, who were matched for BMI (mostly normal weight to overweight) and IQ. Depletion of central dopamine reduced the working memory specific performance on the operation span task (OSPAN) in the LFS, but not in the HFS group (p = 0.023, r = 0.210). Learning from positive and negative reinforcement (probabilistic selection task: PST) was increased in both diet groups after dopamine depletion (p = 0.048, r = 0.144). As secondary exploratory research question we measured peripheral dopamine precursor availability (pDAP) at baseline as an estimate for central dopamine levels. The HFS group had a significantly higher pDAP at baseline compared to the LFS group (p = .048, r = −0.355). Our data provides first evidence that the intake of HFS is associated with changes in indirect measures of central dopamine levels in humans. The observed associations are independent of body weight status, suggesting that consumption of HFS might be associated with maladaptive behaviors contributing to the development of obesity.


2019 ◽  
Author(s):  
Roman Trepp ◽  
Raphaela Muri ◽  
Lenka Bosanska ◽  
Stephanie Abgottspon ◽  
Michel Hochuli ◽  
...  

Abstract Background The population of adult patients with early-treated phenylketonuria (PKU) following newborn screening is growing substantially. The ideal target range of blood Phe levels in adults outside pregnancy is discussed controversially. Therefore, prospective intervention studies are needed to evaluate the effects of an elevated Phe concentration on cognition and structural, functional and neurometabolic parameters of the brain. Methods The PICO (Phenylalanine and Its Impact on Cognition) Study evaluates the effect of a 4-week phenylalanine (Phe) load on cognition and cerebral parameters in 30 adults with early-treated PKU in a double-blind, randomized, placebo-controlled, crossover, non-inferiority trial. The primary objective of the PICO Study is to prospectively assess whether a temporarily elevated Phe level influences cognitive performance in adults with early-treated PKU. As secondary objective, the PICO Study will elucidate cerebral and neurometabolic mechanisms, which accompany changes in Phe concentration using advanced neuroimaging methods. In addition to the intervention study, cognition, structural and functional parameters of the brain of adult patients with early-treated PKU will be cross-sectionally compared to healthy controls, who will be comparable with regard to age, gender and education level. Advanced MR-techniques will be used to investigate intensity of neural activation during the working memory task (fMRI), strength of functional connectivity between brain regions related to performance in working memory (rsfMRI), white matter integrity (DTI), cerebral blood flow (ASL) and brain Phe concentrations (MRS). Discussion Using a combination of neuropsychological and neuroimaging data, the PICO study will considerably contribute to improve the currently insufficient level of evidence on how adult patients with early-treated PKU should be managed.


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