Research reportNear-infrared imaging of the effects of glucose ingestion and regulation on prefrontal activation during dual-task execution in healthy fasting older adults
Highlights
► Glucose ingestion improves older adults’ ability to coordinate concurrent tasks. ► It also increases activation in right ventral–lateral prefrontal regions. ► Variations in glucose regulation modulate glucose effects on behavioral and activation data. ► NIRS is an efficient way to study glucose effects in older adults.
Introduction
Nutrition can exert an acute effect on cognition in older adults, like following a meal [25]. For instance, glucose ingestion can momentarily improve cognition, with documented effects on episodic memory [28], [30]. Recent evidences however also suggest beneficial effects on attentional control. For instance, small rises in blood glucose levels momentarily improved dual-task performances in young adults [31] and in healthy older adults [9]. However, the mechanisms underlying glucose effects on cognition are still misunderstood and very few studies have used neurophysiology or neuroimaging techniques to examine brain activation patterns associated with glucose effects on cognition.
Among the few studies that have used electrophysiology or neuroimaging techniques, some have examined the effects of glucose ingestion on event-related potentials (ERP). For instance, Smith et al. [35] found that glucose ingestion acutely influenced ERP components in healthy adolescents. During a recognition memory task, participants provided faster responses after consuming a glucose drink (25 g) than after a placebo drink (aspartame). Furthermore, in the glucose condition ERP components associated with familiarity and with recollection (FN400 and LP) showed greater amplitude differences between old and new items. Similarly, Riby et al. [29] studied neurocognitive correlates of glucose effects using ERPs in young adults. Participants performed an odd-ball task on two occasions: after a glucose drink (25 g) and after a placebo drink (saccharin). The task required participants to press the response key only when target stimuli appeared on the screen (0.1 probability) and to ignore irrelevant stimuli. Behavioral data failed to reveal an effect of treatment on reaction time or accuracy during task execution. Despite the absence of glucose-effects on behavioral data, EEG results showed that the P3b component, typically associated with memory storage operations, had a smaller amplitude, shorter latency, and duration when participants were in the glucose condition. Moreover, the P3a and P2 components, the more attentional and frontal components, showed no difference between treatment conditions, yet they were more variable when individuals were in the glucose condition. The authors attribute this greater variance to possible individual differences in glucose regulation [29].
Evidence from functional magnetic resonance imaging (fMRI) also suggests that blood glucose levels influence the hemodynamic response, by modulating the blood oxygenation level dependent signal (BOLD). A pilot study performed by Stone et al. [36] examined glucose effects on brain activation in seven participants diagnosed with schizophrenia using fMRI. Participants took part in glucose (50 g) and placebo sessions (saccharin) during which they learned word-pairs that were presented visually. Although participants displayed similar recognition performances during both conditions, activation data significantly differed. In fact, in the glucose condition, participants showed increased activation in the left parahippocampus gyrus and a trend toward greater activation in the left dorsolateral prefrontal cortex during encoding, compared to the placebo condition. Stone et al. explain the lack of glucose effects on behavioral data because of the less demanding nature of recognition compared to free recall. Hence, albeit the relatively small sample and the preliminary nature of these data, it appears that glucose ingestion influences brain activation in individuals with schizophrenia.
Evidence from studies in the field of hypoglycemia also suggests that blood glucose levels can influence the BOLD signal. Anderson et al. [2] compared the BOLD signal during passive sensory stimulation when younger adults were in a hypoglycemic clamp condition to when they were in a euglycemic clamp condition. They observed that hypoglycemia decreased the BOLD signal by 28%, which was reversed when individuals were returned to euglycemia.
The studies reported above suggest that glucose ingestion and more broadly, blood glucose levels influence brain activation. However, none of the previous studies has examined neurocognitive correlates of glucose effects in an older adult population. Moreover, most studies reported so far have used memory tasks and the effects of glucose ingestion on brain activation patterns have not been systematically examined for attentional tasks. Recent studies suggest that small rises in blood glucose levels can improve dual-task performances in young adults [31] and in healthy older adults [9]. Another important aspect to consider is that glucose effects on cognition can be moderated by individual differences in glucose regulation, the ability to clear glucose from the blood stream, which tends to be less efficient in older adults [27]. Therefore, individuals’ capacity to metabolize glucose must be considered when studying the acute effect of glucose on cognition in older adults. For instance, type 2 diabetes and to a lesser extent, pre-diabetes, have been associated with deficits in general cognitive functioning, episodic memory, processing speed, and executive functions [3], [26], [38], [42]. Increasing evidence suggests that even among apparently metabolically healthy older adults, those with poorer glucose regulation show poorer cognitive performances, with decrements in episodic memory being the most commonly reported outcome measure [16] and decrements in attentional control and executive functions also reported [1], [10], [21], [20], [30].
So far, few studies have used brain imaging to investigate acute glucose-effects on brain functions [29], [36] and those that have done so have not taken into account individual differences in glucose regulation. Even though the relationship between activation and glucose regulation has not been systematically studied, Riby et al. [29] observed that the attentional ERP components (P3a and P2) showed more important variance in the glucose condition. This suggests a potential modulation of brain activation related to glucose regulation. The objective of the present study was thus to investigate the neurocognitive correlates of glucose effects on attentional control using functional near-infrared spectroscopy (fNIRS) during dual-task performance. Indeed, dual-task paradigms are en efficient way to assess attentional control and are designed to isolate attentional control processes from processing speed components [4], [5], [7]. Moreover, age-related deficits in divided attention are commonly reported [39], [40] and glucose-effects on dual-task performances have recently been reported in older adults [9]. As for fNIRS, it is a neuroimaging technique that sends light carried by an optical fiber through the scalp. The light emitted by the source diffuses through the skin, skull, and cortex, and is then captured by detectors placed a few centimeters from the source. Oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) are two chromophores absorbing light, and thus changes in light intensity allows to measure changes in their relative concentration following activation related to a task [11], [18]. fNIRS is an effective method to study executive functions and frontally mediated tasks such as the Stroop task, switching tasks, as well as verbal fluency tasks [13], [17], [32]. Of particular interest for the present study, fNIRS has been used in older adults and has showed age-related changes in brain activation related to attentional control performances [33]. To summarize, these studies suggest that glucose ingestion can momentarily improve attentional control in older adults [9], [28], yet the neurophysiological correlates of these glucose effects are not yet fully understood. The few studies that have used neuroimaging suggest that glucose ingestion can influence brain activation [29], [36], however the activation correlates for attentional control tasks have not yet been studied. Moreover, most studies have been performed in younger adults and brain activation patterns associated with glucose ingestion have been understudied in older adults. Finally, past studies have not taken into account individual differences in glucose regulation, which becomes less efficient with increasing age, and has been associated with attentional control performances in non-diabetic older adults [10], [27]. Hence, our study had two main objectives: (i) determining the acute effects of glucose ingestion on prefrontal activation during dual-task execution in older adults; (ii) examining the influence of glucose regulation on prefrontal activation and dual-task performances. To realize these objectives we measured prefrontal activation using fNIRS while participants performed an event-related dual-task test and compared activation following a glucose drink and following a placebo unsweetened drink. Based on Gagnon et al. [9], we hypothesized that individuals would perform better on the dual-task when they are in the glucose condition, more specifically; show a reduced dual-task cost. These better performances in the glucose condition relative to the placebo condition should be associated with differential activation in the prefrontal regions. Finally, based on a previous study we can expect that poorer regulators will obtain poorer dual-task performances compared to better regulators [10]. Individual differences in glucose regulation should thus correlate with dual-task performances and dual-task related prefrontal activation.
Section snippets
Participants
Twenty non-diabetic adults aged 60 years and older (Mage = 69.4years, Meducation = 15.8years, 16 women, 4 men) took part in the study. All were community-dwelling individuals, who gave their informed consent to participate. The study was approved by the research center's ethics board. Participants were recruited from newspaper ads and flyers posted in community centers and libraries. A phone interview was then administered to insure that participants did not have diabetes and did not present
Results
Statistical analyses were conducted with PAWS 18.0 (Chicago, Illinois), which provides adjusted alpha levels (Huynh–Feldt) for within-subject factors to correct for violations of homogeneity of variance. Preliminary analyses showed that data were normally distributed. However, one outlier was found for behavioral data and was excluded from further analyses (more than 2 SD from the group mean). Moreover, from the 20 initial participants in the study, data from 4 were eliminated due to excessive
Discussion
This study explored the effects of glucose ingestion on dual-task performances and on prefrontal brain activation patterns underlying these effects. A second issue that was addressed by this study was related to the way individual differences in glucose regulation could moderate glucose effects on dual-task performances and on prefrontal activation patterns. A counterbalanced within-subjects design was used in which participants performed an event-related dual-task while prefrontal activation
Acknowledgments
This research was supported by a scientist fellowship from the Fonds de Recherche en Santé du Québec and a discovery grant from the Natural Sciences and Engineering Research Council of Canada to L.B. and by a fellowship from the Canadian Institutes of Health Research to C.G. The authors would like to thank participants for their involvement in this study.
References (42)
- et al.
The effects of glucose on nonmemory cognitive functioning in the elderly
Neuropsychologia
(1996) - et al.
Effects of hypoglycemia on human brain activation measured with fMRI
Magn Reson Imaging
(2006) - et al.
Neural correlates of dual-task performance after minimizing task-preparation
Neuroimage
(2005) - et al.
Training-induced plasticity in older adults: effects of training on hemispheric asymmetry
Neurobiol Aging
(2007) - et al.
Mini-mental state. A practical method for grading the cognitive state of patients for the clinician
J Psychiatr Res
(1975) - et al.
Cognitive performance is associated with glucose regulation in healthy elderly persons and can be enhanced with glucose and dietary carbohydrates
Am J Clin Nutr
(2000) - et al.
Impairments in glucose tolerance can have a negative impact on cognitive function: a systematic research review
Neurosci Biobehav Rev
(2009) - et al.
The hemodynamics of cognitive control: the level of concentration of oxygenated hemoglobin in the superior prefrontal cortex varies as a function of performance in a modified Stroop task [Clinical Trial Research Support, Non-U.S. Gov’t]
Behav Brain Res
(2008) Glucose improvement of memory: a review
Eur J Pharmacol
(2004)- et al.
Effect of age and glucoregulation on cognitive performance
Neurobiol Aging
(2003)
Glucose regulation is associated with cognitive performance in young nondiabetic adults
Behav Brain Res
Three-dimensional probabilistic anatomical cranio-cerebral correlation via the international 10–20 system oriented for transcranial functional brain mapping
Neuroimage
The assessment and analysis of handedness: the Edinburgh inventory
Neuropsychologia
Prefrontal activation due to Stroop interference increases during development—an event-related fNIRS study
Neuroimage
Medial temporal and prefrontal lobe activation during verbal encoding following glucose ingestion in schizophrenia: a pilot fMRI study
Neurobiol Learn Mem
The glycemic index: methodology and clinical implications
Am J Clin Nutr
The relationship between impaired glucose tolerance, type 2 diabetes, and cognitive function
J Clin Exp Neuropsychol
Training effects on dual-task performance: are there age-related differences in plasticity of attentional control?
Psychol Aging
Transfer effects in task-set cost and dual-task cost after dual-task training in older and younger adults: further evidence for cognitive plasticity in attentional control in late adulthood
Exp Aging Res
The acute effects of glucose ingestion on attentional control in fasting healthy older adults
Psychopharmacology (Berl)
Glucose regulation is associated with attentional control performances in non-diabetic older adults
J Clin Exp Neuropsychol
Cited by (23)
Advancing age, influence of dietary sugars, salts, and fats on chronic diseases and metabolic disorders
2020, Dietary Sugar, Salt and Fat in Human HealthUse of near-infrared spectroscopy in the investigation of brain activation during cognitive aging: A systematic review of an emerging area of research
2017, Ageing Research ReviewsCitation Excerpt :Finally, acute or transient manipulations of the experimental conditions can influence brain hemodynamic patterns. NIRS studies with older adults have shown that acute physical exercise (Hyodo et al., 2012; Lucas et al., 2012) or glucose ingestion (Gagnon et al., 2012) may improve cognitive performance and increase PFC brain activation, as measured by variations of oxy-deoxy or total-hemoglobin relative concentrations. However, the interaction between cognitive and brain activation is complex during acute physical exercise and is influenced by several factors, such as exercise intensity, exercise duration, task difficulty, fitness level of subjects, aging and health status (see Ando, 2016).
The effect of carbohydrate and protein co-ingestion on energy substrate metabolism, sense of effort, and affective responses during prolonged strenuous endurance exercise
2017, Physiology and BehaviorCitation Excerpt :As cortisol is considered an indicator of distress and negative affect [7], an increase in cortisol in response to the decreasing BG level may also be attributable to the negative affect associated with low BG. Functional near-infrared imaging studies have found an association between BG elevation and increases in the hemodynamic response in the brain [33] and blood oxygenation [34]. The abovementioned neurobiological evidence suggests potential physiological basements for affective responses following CHO ingestion.
Utilizing slope method as an alternative data analysis for functional near-infrared spectroscopy-derived cerebral hemodynamic responses
2013, International Journal of Industrial ErgonomicsCitation Excerpt :Usually, the magnitude of the cortical activation level relies on the significance of data changes (i.e., pre-stimulation vs. stimulation) (Gervain et al., 2011). Commonly, the main variables of interest calculated to depict the fNIRS activation pattern are: difference of oxy-Hb and deoxy-Hb signal changes (Izzetoglu et al., 2004); sum of oxy-Hb and deoxy-Hb signal changes (Izzetoglu et al., 2004; Gervain et al., 2011); area under the curve (Limongi et al., 2009; Gagnon et al., 2012); Z-score (Tsunashima et al., 2012); amplitude response for oxy-Hb and deoxy-Hb (Perrey, 2008; Holper et al., 2009; Gervain et al., 2011) by comparing a baseline period to (i) the largest response obtained during a suitable temporal window during the stimulation period (Colier et al., 1999; Gervain et al., 2011) or (ii) the mean activation values measured throughout task (Tanida et al., 2004, 2007, 2008). However, the field of fNIRS still suffers from the lack of a commonly accepted standard by which investigators could describe and compare activation magnitudes.