Impaired neurovascular coupling in metabolic syndrome: an fNIRS study

Abstract

The mechanisms underpinning accelerated cognitive decline in metabolic syndrome (MetS) are poorly understood. Neurovascular coupling (NVC) is the coordinated matching of blood flow to neuronal activation and is dependent on endothelial function. NVC may drive blood flow dysregulation that contributes to neuronal damage and cognitive decline. The purpose was to assess NVC, peripheral endothelial function, and cognitive performance in older adults with MetS and healthy controls (CON), and the association of these factors. Older adults with and without MetS were recruited to complete a neurocognitive battery, assessment of NVC, and endothelial function. NVC was measured in the frontoparietal regions using functional near infrared spectroscopy (fNIRS) while participants completed the n-back task (0-, 1-, 2-back). Changes in oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) signals reflected NVC during the n-back task. Endothelial function was measured using brachial ultrasound measurements of flow-mediated dilation (%FMD). MetS (n = 22; age: 66 ± 6 yr) demonstrated poorer NVC during higher cognitive loads, reflected by an attenuated increase in HbO in the premotor cortex during the 2-back task compared with CON (n = 26; age: 64 ± 5 yr) (P = 0.036). MetS also demonstrated poorer FMD (5.55 ± 1.35% vs. 4.42 ± 1.71%, P = 0.01) and 2-back accuracy compared with CON (MetS: 81.7 ± 6.4%; CON: 86.0 ± 6.1%, P = 0.027), with a significant positive association between these two factors (r = 0.37, P = 0.012). Impairments in NVC of the frontal cortex may be an early cerebrovascular mechanism underpinning cognitive decline in MetS and is discernible during higher cognitive loads. Peripheral endothelial dysfunction may be implicated in this mechanism.NEW & NOTEWORTHY Deficits in neurovascular coupling (NVC) precede neuronal damage and subsequent cognitive deficits, encompassing the vascular contributions to cognitive decline framework. Older adults with metabolic syndrome (MetS), a prevalent population, present with accelerated cognitive decline, however, changes to NVC in MetS had not been studied. We demonstrate that older adults with MetS exhibit reduced NVC during higher cognitive loads compared with healthy older adults, which corresponds with poorer working memory performance, and may involve endothelial dysfunction.

Keywords: VCID; cerebrovascular; cognition; metabolic syndrome; neurovascular coupling.

Figure 1:. Neurovascular coupling and n-back task instrumentation and design.

A. Visual n-back letter task with 3 conditions illustrated (0-, 1-, 2-back). Shaded boxes indicate target letters for each condition. Dotted arrows indicate the letter that the target is based off of, X number of letter(s) back. Target for 0-back was just a specified letter (Z), for 1-back was any letter that was shown 1 letter previous, for 2-back was any letter that was shown 2 letters previously. Each n-back task block lasted 60 seconds continuously, with a 60 second rest period between blocks. B. Neurovascular coupling assessment instrumentation and setup. ISI = inter-stimulus interval.

Figure 2:. fNIRS montage and sensitivity map and corresponding cortical regions.

A: Sensitivity profiles were generated from precalculated fluence profiles using AtlasViewer (Aasted 2016); B: (A) premotor cortex (PMC); (B) dorsolateral prefrontal cortex (dlPFC); (C) medial prefrontal cortex (mPFC); (D) frontopolar areas (OFC); Regions were designated according to Brodmann’s map-based sensitivity profiles generated by the fOLD software (Morais 2018).

Figure 3:. MetS exhibit poorer endothelial function and greater arterial stiffness compared to CON.

Group differences in allosterically corrected FMD (A) and baPWV (B) between MetS (n=22) and CON (n=26). * p < 0.05. FMD = flow mediated dilation; baPWV = brachial-ankle pulse wave velocity.

Figure 4:. Neurovascular coupling response during the n-back task by group and condition.

(A): Changes in HbO from resting baseline. Significant main effects of ‘condition’, ‘region’, and ‘group’ (p<0.05), Mean HbO in the PMC region was significantly lower in MetS compared to CON in the 2-back task (p=0.036). Black box = group differences, units on the color bar represent change in HbO [ΔM cm]. (B): Changes in HbR from resting baseline. The fOLD software [Morais 2018] was utilized to determine brain regions based on the 10-20 International system and Brodmann’s map areas. Sensitivity and specificity of each channel in the montage map to Brodmann’s map regions were calculated and channels corresponding to dorsolateral prefrontal cortex (dlPFC), medial prefrontal cortex (mPFC), premotor cortex (PMC), and orbitofrontal cortex (OFC) were averaged.

Figure 4:. Neurovascular coupling response during the n-back task by group and condition.

(A): Changes in HbO from resting baseline. Significant main effects of ‘condition’, ‘region’, and ‘group’ (p<0.05), Mean HbO in the PMC region was significantly lower in MetS compared to CON in the 2-back task (p=0.036). Black box = group differences, units on the color bar represent change in HbO [ΔM cm]. (B): Changes in HbR from resting baseline. The fOLD software [Morais 2018] was utilized to determine brain regions based on the 10-20 International system and Brodmann’s map areas. Sensitivity and specificity of each channel in the montage map to Brodmann’s map regions were calculated and channels corresponding to dorsolateral prefrontal cortex (dlPFC), medial prefrontal cortex (mPFC), premotor cortex (PMC), and orbitofrontal cortex (OFC) were averaged.

Figure 5:. NVC responses in the PMC and dlPFC during the 2-back task.

A. 3D topographic map of HbO responses in MetS compared to CON. B. Mean HbO responses in PMC and dlPFC during the 2-back task (95% CI). Temporal data are presented across the entire 60s task duration for all participants in the MetS (n=22) and CON (n=26). PMC = Premotor Cortex, dlPFC = dorsolateral prefrontal cortex. P-values are for comparisons in average HbO changes between MetS and CON in each the PMC and dlPFC.

Figure 6:. Positive association between FMD and 2-back Accuracy in older adults with and without MetS.

Data are presented using the Pearson correlation coefficient. FMD = flow mediated dilation.