Physical Activity Is Linked to Greater Moment-To-Moment Variability in Spontaneous Brain Activity in Older Adults

<div><p>Higher cardiorespiratory fitness (CRF) and physical activity (PA) in old age are associated with greater brain structural and functional integrity, and higher cognitive functioning. However, it is not known how different aspects of lifestyle such as sedentariness, light PA (LI-PA), or moderate-to-vigorous physical activity (MV-PA) relate to neural activity in aging. In addition, it is not known whether the effects of PA on brain function differ or overlap with those of CRF. Here, we objectively measured CRF as oxygen consumption during a maximal exercise test and measured PA with an accelerometer worn for 7 days in 100 healthy but low active older adults (aged 60–80 years). We modeled the relationships between CRF, PA, and brain functional integrity using multivariate partial least squares analysis. As an index of functional brain integrity we used spontaneous moment-to-moment variability in the blood oxygenation level-dependent signal (SD_BOLD), known to be associated with better cognitive functioning in aging. We found that older adults who engaged more in LI-PA and MV-PA had greater SD_BOLD in brain regions that play a role in integrating segregated functional domains in the brain and benefit from greater CRF or PA, such as precuneus, hippocampus, medial and lateral prefrontal, and temporal cortices. Our results suggest that engaging in higher intensity PA may have protective effects on neural processing in aging. Finally, we demonstrated that older adults with greater overall WM microstructure were those showing more LI-PA and MV-PA and greater SD_BOLD. We conclude that SD_BOLD is a promising correlate of functional brain health in aging. Future analyses will evaluate whether SD_BOLD is modifiable with interventions aimed to increase PA and CRF in older adults.</p></div

Significant clusters representing the CRF/PA—SD_BOLD model from Fig 1.

<p>All peaks and clusters were determined using a voxel extent ≥10, minimum distance 10mm, and bootstrap ratio (BSR) ≥3.00. MNI, Montreal Neurological Institute (mm). R: right; L: left; IFG: inferior frontal gyrus, FP: frontal pole; mPFC: medial prefrontal cortex, SFG: superior frontal gyrus; TP: temporal pole; STG: superior temporal gyrus; pOPER: parietal operculum; SMG: supramarginal gyrus, lat: lateral; OCCIP: occipital cortex; IPC: intraparietal cortex; PCG: post central gyrus; M1: primary motor cortex; SPL: superior parietal lobule; ACC: anterior cingulate cortex; SMA: supplementary motor area; V3/V4: visual cortex III, IV; V1: primary visual cortex; HIPP: hippocampus; ITG: inferior temporal gyrus; V2: secondary visual area; PPC: posterior parietal cortex.</p><p>Significant clusters representing the CRF/PA—SD_BOLD model from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0134819#pone.0134819.g001" target="_blank">Fig 1</a>.</p

Descriptive statistics and correlations with age.

<p>*Raw data.</p><p>** MV-PA were ln-transformed for correlations with age. There were gender differences only for CRF and not for any other variables.</p><p>Descriptive statistics and correlations with age.</p

Multivariate relationships between CRF, PA, and SD_BOLD (the CRF/PA—SD_BOLD model).

<p><b>A:</b> PLS spatial pattern of the CRF/PA—SD_BOLD model. Red-yellow regions indicate greater SD_BOLD with greater LI-PA and MV-PA. Significant regions: bootstrap ratio ≥3.00. Abbreviations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0134819#pone.0134819.t002" target="_blank">Table 2</a>. <b>B:</b> Correlation magnitudes (Pearson r) between CRF, sedentary time, LI-PA, MV-PA, and SD_BOLD during rest (permuted p<0.001, error bars represent bootstrapped 95% confidence intervals). CRF and sedentary time did not contribute to the LV as their error bars cross zero.</p

Caudate Nucleus Volume Mediates the Link between Cardiorespiratory Fitness and Cognitive Flexibility in Older Adults.

<p>The basal ganglia play a central role in regulating the response selection abilities that are critical for mental flexibility. In neocortical areas, higher cardiorespiratory fitness levels are associated with increased gray matter volume, and these volumetric differences mediate enhanced cognitive performance in a variety of tasks. Here we examine whether cardiorespiratory fitness correlates with the volume of the subcortical nuclei that make up the basal ganglia and whether this relationship predicts cognitive flexibility in older adults. Structural MRI was used to determine the volume of the basal ganglia nuclei in a group of older, neurologically healthy individuals (mean age 66 years, N = 179). Measures of cardiorespiratory fitness (VO(2max)), cognitive flexibility (task switching), and attentional control (flanker task) were also collected. Higher fitness levels were correlated with higher accuracy rates in the Task Switching paradigm. In addition, the volume of the caudate nucleus, putamen, and globus pallidus positively correlated with Task Switching accuracy. Nested regression modeling revealed that caudate nucleus volume was a significant mediator of the relationship between cardiorespiratory fitness, and task switching performance. These findings indicate that higher cardiorespiratory fitness predicts better cognitive flexibility in older adults through greater grey matter volume in the dorsal striatum.</p

Physical Activity and Cardiorespiratory Fitness Are Beneficial for White Matter in Low-Fit Older Adults

<div><p>Physical activity (PA) and cardiorespiratory fitness (CRF) are associated with better cognitive function in late life, but the neural correlates for these relationships are unclear. To study these correlates, we examined the association of both PA and CRF with measures of white matter (WM) integrity in 88 healthy low-fit adults (age 60–78). Using accelerometry, we objectively measured sedentary behavior, light PA, and moderate to vigorous PA (MV-PA) over a week. We showed that greater MV-PA was related to lower volume of WM lesions. The association between PA and WM microstructural integrity (measured with diffusion tensor imaging) was region-specific: light PA was related to temporal WM, while sedentary behavior was associated with lower integrity in the parahippocampal WM. Our findings highlight that engaging in PA of various intensity in parallel with avoiding sedentariness are important in maintaining WM health in older age, supporting public health recommendations that emphasize the importance of active lifestyle.</p></div

Regression models predicting WM integrity.

<p>CRF data is in units of mL/kg/min, Sedentary and MV-PA are expressed in hours (ln-transformed for MV-PA).</p><p>Regression models predicting WM integrity.</p

Partial correlations between CRF and levels of PA.

<p>All correlations controlled for age and gender. pr denotes partial correlation. CRF data is in units of mL/kg/min, Sedentary, Light, and MV-PA are expressed in hours (ln-transformed for MV-PA, winsorized for valid hours).</p><p>Partial correlations between CRF and levels of PA.</p

Illustration of WMH volume and FA analyses.

<p>A: An example of segmentation of WMHs on a T2-weighted image. B: Regions of interest for DTI analysis. Mean WM skeleton overlaid on FMRIB58_FA mean FA image. Anterior corpus callosum (antCC), anterior cingulum (antCING), superior longitudinal fasciculus (SLF), temporal lobe WM (TEMP), and parahippocampal WM (paraHIPP). C: Scatterplots showing the representative relationships between PA, CRF, and WM integrity. *Indicates that the variable was ln-transformed.</p

Variables of interest: descriptive statistics and correlations with age.

<p>*Raw data.</p><p>** WMH and MV-PA were ln-transformed for correlations with age and valid hours were winsorized.</p><p>*** The values are after excluding two outliers >2.5 SD.</p><p>Variables of interest: descriptive statistics and correlations with age.</p